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Transglutaminases: Expression in Kidney and Relation to Kidney Fibrosis

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Transglutaminases

Abstract

Kidney fibrosis is regarded as a chronic wound response and tissue remodeling process consequent to a persistent tissue damage. The fibrosis is characterized by excessive extracellular matrix accumulation, fibroblast proliferation and chronic inflammation that leads to loss of tissue architecture and function. Transglutaminase-2 (TG2) is an essential component of wound repair and overexpression of TG2 and/or excessive crosslinking by TG2 have been notably linked to the pathogenesis of fibrosis in various organs. In this chapter, we discuss chronic kidney disease as one of the most prevalent chronic diseases, whose characteristic trait is fibrosis. We attempt to review recent thinking on the cellular and molecular causes of kidney fibrosis and review studies linking the role and enzymatic activity of TG2 with the pathogenesis of kidney fibrosis. Additionally we discuss how TG2 represents a new treatment target, which has catalyzed advances in the treatment of kidney disease.

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References

  • Aeschlimann D, Thomazy V (2000) Protein crosslinking in assembly and remodelling of extracellular matrices: the role of transglutaminases. Connect Tissue Res 41(1):1–27

    Article  CAS  PubMed  Google Scholar 

  • Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH (2013) Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol 24(2):302–308. doi:10.1681/ASN.2012070718 ASN.2012070718 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Akimov SS, Krylov D, Fleischman LF, Belkin AM (2000) Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 148(4):825–838

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Alhasan AA, Spielhofer J, Kusche-Gullberg M, Kirby JA, Ali S (2014) Role of 6-O-sulfated heparan sulfate in chronic renal fibrosis. J Biol Chem 289(29):20295–20306. doi:10.1074/jbc.M114.554691 M114.554691 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ali S, Hardy LA, Kirby JA (2003) Transplant immunobiology: a crucial role for heparan sulfate glycosaminoglycans? Transplantation 75(11):1773–1782. doi:10.1097/01.TP.0000065805.97974.93

    Article  CAS  PubMed  Google Scholar 

  • Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGFbeta activation. J Cell Sci 116(Pt 2):217–224

    Article  CAS  PubMed  Google Scholar 

  • Balklava Z, Verderio E, Collighan R, Gross S, Adams J, Griffin M (2002) Analysis of tissue transglutaminase function in the migration of Swiss 3T3 fibroblasts: the active-state conformation of the enzyme does not affect cell motility but is important for its secretion. J Biol Chem 277(19):16567–16575. doi:10.1074/jbc.M109836200. doi:10.1074/jbc.M109836200 M109836200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Bishop JR, Schuksz M, Esko JD (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446(7139):1030–1037. doi:nature05817 [pii] 10.1038/nature05817

    Article  CAS  PubMed  Google Scholar 

  • Boor P, Ostendorf T, Floege J (2010) Renal fibrosis: novel insights into mechanisms and therapeutic targets. Nat Rev Nephrol 6(11):643–656. doi:10.1038/nrneph.2010.120 nrneph.2010.120 [pii]

    Article  PubMed  Google Scholar 

  • Bowness JM, Folk JE, Timpl R (1987) Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen. J Biol Chem 262(3):1022–1024

    CAS  PubMed  Google Scholar 

  • Broekhuizen LN, Lemkes BA, Mooij HL, Meuwese MC, Verberne H, Holleman F, Schlingemann RO, Nieuwdorp M, Stroes ES, Vink H (2010) Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia 53(12):2646–2655. doi:10.1007/s00125-010-1910-x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burhan IW, Nutter FH, Johnson TS, Verderio E (2011) Association of Transglutaminase-2 and Syndecan-4 in the 5/6th subtotal nephrectomy (SNx) rat model of progressive renal scarring. In: Proceedings of the Renal Association (joint with British Renal Society) Congress-Birmingham, UK

    Google Scholar 

  • Campbell RA (1987) Polyamines and uremia. Adv Exp Med Biol 223:47–54

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Gao B, Huang C, Olsen B, Rotundo RF, Blumenstock F, Saba TM (2000) Transglutaminase-mediated fibronectin multimerization in lung endothelial matrix in response to TNF-alpha. Am J Physiol Lung Cell Mol Physiol 279(1):L161–L174

    CAS  PubMed  Google Scholar 

  • Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J (2004) The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 140(3):167–174. doi:140/3/167 [pii]

    Article  PubMed  Google Scholar 

  • Chen D, Huang HC, Yu L (2005) [Expression and implication of tissue transglutaminase and connective tissue growth factor at fibrotic tubulointerstitium in kidneys from UUO rats]. Beijing Da Xue Xue Bao 37(2):143–146

    CAS  PubMed  Google Scholar 

  • Chen NX, O’Neill K, Chen X, Kiattisunthorn K, Gattone VH, Moe SM (2013) Transglutaminase 2 accelerates vascular calcification in chronic kidney disease. Am J Nephrol 37(3):191–198. doi:10.1159/000347031 000347031 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Cheng S, Pollock AS, Mahimkar R, Olson JL, Lovett DH (2006) Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. FASEB J 20(11):1898–1900. doi:fj.06-5898fje [pii] 10.1096/fj.06-5898fje

    Article  CAS  PubMed  Google Scholar 

  • Chou CY, Streets AJ, Watson PF, Huang L, Verderio EA, Johnson TS (2011) A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal beta-sandwich domain. J Biol Chem 286(31):27825–27835. doi:10.1074/jbc.M111.226340 M111.226340 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clayton A, Thomas J, Thomas GJ, Davies M, Steadman R (2001) Cell surface heparan sulfate proteoglycans control the response of renal interstitial fibroblasts to fibroblast growth factor-2. Kidney Int 59(6):2084–2094

    Article  CAS  PubMed  Google Scholar 

  • Colvin RB (2003) Chronic allograft nephropathy. N Engl J Med 349(24):2288–2290. doi:10.1056/NEJMp038178 349/24/2288 [pii]

    Article  CAS  PubMed  Google Scholar 

  • da Silva Lodge M ENM, Johnson TS (2013) Urinary transglutaminase 2 as a potential biomarker of chronic kidney disease detection and progression. Lancet 381(Supplement 1 (Spring Meeting for Clinician Scientists in Training, 27 February 2013)):S33 Poster Abstract

    Google Scholar 

  • Dane M, van den Berg B, Rabelink T (2014) The endothelial glycocalyx: scratching the surface for cardiovascular disease in kidney failure. Atherosclerosis 235(1):56–57. doi:10.1016/j.atherosclerosis.2014.04.005 S0021-9150(14)00204-4 [pii]

    Article  CAS  PubMed  Google Scholar 

  • De Laurenzi V, Melino G (2001) Gene disruption of tissue transglutaminase. Mol Cell Biol 21(1):148–155. doi:10.1128/MCB.21.1.148-155.2001

    Article  PubMed Central  PubMed  Google Scholar 

  • Deasey S, Shanmugasundaram S, Nurminskaya M (2013) Tissue-specific responses to loss of transglutaminase 2. Amino Acids 44(1):179–187. doi:10.1007/s00726-011-1183-9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Devuyst O, Antignac C, Bindels RJ, Chauveau D, Emma F, Gansevoort R, Maxwell PH, Ong AC, Remuzzi G, Ronco P, Schaefer F (2012) The ERA-EDTA Working Group on inherited kidney disorders. Nephrol Dial Transplant 27(1):67–69. doi:10.1093/ndt/gfr764 gfr764 [pii]

    Article  PubMed  Google Scholar 

  • Docherty NG, Calvo IF, Quinlan MR, Perez-Barriocanal F, McGuire BB, Fitzpatrick JM, Watson RW (2009) Increased E-cadherin expression in the ligated kidney following unilateral ureteric obstruction. Kidney Int 75(2):205–213. doi:10.1038/ki.2008.482 ki2008482 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Duffield JS (2014) Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest 124(6):2299–2306. doi:10.1172/JCI72267 72267 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kottgen A, Levey AS, Levin A (2013) Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 382(9887):158–169. doi:10.1016/S0140-6736(13)60439-0 S0140-6736(13)60439-0 [pii]

    Article  PubMed  Google Scholar 

  • El Nahas AM, Abo-Zenah H, Skill NJ, Bex S, Wild G, Griffin M, Johnson TS (2004) Elevated epsilon-(gamma-glutamyl)lysine in human diabetic nephropathy results from increased expression and cellular release of tissue transglutaminase. Nephron Clin Pract 97(3):c108–c117. doi:10.1159/000078639 78639 [pii]

    Article  PubMed  Google Scholar 

  • el-Khatib MT, Becker GJ, Kincaid-Smith PS (1987) Morphometric aspects of reflux nephropathy. Kidney Int 32(2):261–266

    Article  CAS  PubMed  Google Scholar 

  • Fan Q, Shike T, Shigihara T, Tanimoto M, Gohda T, Makita Y, Wang LN, Horikoshi S, Tomino Y (2003) Gene expression profile in diabetic KK/Ta mice. Kidney Int 64(6):1978–1985

    Article  CAS  PubMed  Google Scholar 

  • Fisher M, Jones RA, Huang L, Haylor JL, El Nahas M, Griffin M, Johnson TS (2009) Modulation of tissue transglutaminase in tubular epithelial cells alters extracellular matrix levels: a potential mechanism of tissue scarring. Matrix Biol 28(1):20–31. doi:10.1016/j.matbio.2008.10.003 S0945-053X(08)00732-4 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Freund KF, Doshi KP, Gaul SL, Claremon DA, Remy DC, Baldwin JJ, Pitzenberger SM, Stern AM (1994) Transglutaminase inhibition by 2-[(2-oxopropyl)thio]imidazolium derivatives: mechanism of factor XIIIa inactivation. Biochemistry 33(33):10109–10119

    Article  CAS  PubMed  Google Scholar 

  • Furini G, Schroeder N, Huang L, Boocock D, Johnson TS, Verderio, EAM (2015) Quantitative proteomics by SWATH-MS reveals an endosomal transport hub of proteins which interact with TG2 in a model of experimental kidney fibrosis. Nephrol Dial Transplant 30(3 (Abstr)):FP013 (ERA-EDTA 052nd Congress, London, 28–31 May 2015)

    Google Scholar 

  • Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, Matsushita K, Wen CP (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382(9889):339–352. doi:10.1016/S0140-6736(13)60595-4 S0140-6736(13)60595-4 [pii]

    Article  PubMed  Google Scholar 

  • Grenard P, Bresson-Hadni S, El Alaoui S, Chevallier M, Vuitton DA, Ricard-Blum S (2001) Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis. J Hepatol 35(3):367–375

    Article  CAS  PubMed  Google Scholar 

  • Griffin M, Coutts IG, Saint R (2004) Novel compounds and methods of using the same. World Patent WO 2004/113363 A2

    Google Scholar 

  • Griffin M, Wilson J (1984) Detection of epsilon(gamma-glutamyl) lysine. Mol Cell Biochem 58(1–2):37–49

    Article  CAS  PubMed  Google Scholar 

  • Griffin M, Smith LL, Wynne J (1979) Changes in transglutaminase activity in an experimental model of pulmonary fibrosis induced by paraquat. Br J Exp Pathol 60(6):653–661

    PubMed Central  CAS  PubMed  Google Scholar 

  • Harrison CA, Layton CM, Hau Z, Bullock AJ, Johnson TS, MacNeil S (2007) Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin. Br J Dermatol 156(2):247–257. doi:BJD7641 [pii] 10.1111/j.1365-2133.2006.07641.x

    Article  CAS  PubMed  Google Scholar 

  • Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RG, Eckardt KU, Kasiske BL, McCullough PA, Passman RS, DeLoach SS, Pun PH, Ritz E (2011) Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 80(6):572–586. doi:10.1038/ki.2011.223 ki2011223 [pii]

    Article  PubMed  Google Scholar 

  • Hewitson TD (2009) Renal tubulointerstitial fibrosis: common but never simple. Am J Physiol Renal Physiol 296(6):F1239–F1244. doi:10.1152/ajprenal.90521.2008 90521.2008 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Hiiragi T, Sasaki H, Nagafuchi A, Sabe H, Shen SC, Matsuki M, Yamanishi K, Tsukita S (1999) Transglutaminase type 1 and its cross-linking activity are concentrated at adherens junctions in simple epithelial cells. J Biol Chem 274(48):34148–34154

    Article  CAS  PubMed  Google Scholar 

  • Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS (2009) Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med 169(4):342–350. doi:10.1001/archinternmed.2008.605 169/4/342 [pii]

    Article  PubMed Central  PubMed  Google Scholar 

  • Huang L, Haylor JL, Hau Z, Jones RA, Vickers ME, Wagner B, Griffin M, Saint RE, Coutts IG, El Nahas AM, Johnson TS (2009) Transglutaminase inhibition ameliorates experimental diabetic nephropathy. Kidney Int 76(4):383–394. doi:ki2009230 [pii] 10.1038/ki.2009.230

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Haylor JL, Fisher M, Hau Z, El Nahas AM, Griffin M, Johnson TS (2010) Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy? Nephrol Dial Transplant 25(12):3897–3910. doi:10.1093/ndt/gfq291. doi:10.1093/ndt/gfq291 gfq291 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Scarpellini A, Funck M, Verderio EA, Johnson TS (2013) Development of a chronic kidney disease model in C57BL/6 mice with relevance to human pathology. Nephron Extra 3(1):12–29. doi:10.1159/000346180 nne-0003-0012 [pii]

    Article  PubMed Central  PubMed  Google Scholar 

  • Iismaa SE, Mearns BM, Lorand L, Graham RM (2009) Transglutaminases and disease: lessons from genetically engineered mouse models and inherited disorders. Physiol Rev 89(3):991–1023. doi:10.1152/physrev.00044.2008 89/3/991 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Ikee R, Kobayashi S, Hemmi N, Saigusa T, Namikoshi T, Yamada M, Imakiire T, Kikuchi Y, Suzuki S, Miura S (2007) Involvement of transglutaminase-2 in pathological changes in renal disease. Nephron Clin Pract 105(3):c139–c146. doi:10.1159/000098646. doi:000098646 [pii] 10.1159/000098646

    Article  CAS  PubMed  Google Scholar 

  • Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Tsuzuki S, Nakamura E, Kusugami K, Saito H, Muramatsu T (2000) Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions. J Biol Chem 275(8):5249–5252

    Article  CAS  PubMed  Google Scholar 

  • Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Iwase M, Yoshikai Y, Yanada M, Yamamoto K, Matsushita T, Nishimura M, Kusugami K, Saito H, Muramatsu T (2001) Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice. J Biol Chem 276(50):47483–47488. doi:10.1074/jbc.M106268200 M106268200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Johnson TS, Griffin M, Thomas GL, Skill J, Cox A, Yang B, Nicholas B, Birckbichler PJ, Muchaneta-Kubara C, Meguid El Nahas A (1997) The role of transglutaminase in the rat subtotal nephrectomy model of renal fibrosis. J Clin Invest 99(12):2950–2960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson TS, Scholfield CI, Parry J, Griffin M (1998) Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas. Biochem J 331(Pt 1):105–112

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson TS, Skill NJ, El Nahas AM, Oldroyd SD, Thomas GL, Douthwaite JA, Haylor JL, Griffin M (1999) Transglutaminase transcription and antigen translocation in experimental renal scarring. J Am Soc Nephrol 10(10):2146–2157

    CAS  PubMed  Google Scholar 

  • Johnson TS, El-Koraie AF, Skill NJ, Baddour NM, El Nahas AM, Njloma M, Adam AG, Griffin M (2003) Tissue transglutaminase and the progression of human renal scarring. J Am Soc Nephrol 14(8):2052–2062

    Article  CAS  PubMed  Google Scholar 

  • Johnson TS, Abo-Zenah H, Skill JN, Bex S, Wild G, Brown CB, Griffin M, El Nahas AM (2004) Tissue transglutaminase: a mediator and predictor of chronic allograft nephropathy? Transplantation 77(11):1667–1675. doi:00007890-200406150-00009 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Johnson TS, Fisher M, Haylor JL, Hau Z, Skill NJ, Jones R, Saint R, Coutts I, Vickers ME, El Nahas AM, Griffin M (2007) Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease. J Am Soc Nephrol 18(12):3078–3088. doi:ASN.2006070690 [pii] 10.1681/ASN.2006070690

    Article  CAS  PubMed  Google Scholar 

  • Jones RA, Nicholas B, Mian S, Davies PJ, Griffin M (1997) Reduced expression of tissue transglutaminase in a human endothelial cell line leads to changes in cell spreading, cell adhesion and reduced polymerisation of fibronectin. J Cell Sci 110(Pt 19):2461–2472

    CAS  PubMed  Google Scholar 

  • K/DOQI (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–266. doi:S0272638602093563 [pii]

    Google Scholar 

  • Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J, Patterson N, Tandon A, Powe NR, Fink NE, Sadler JH, Weir MR, Abboud HE, Adler SG, Divers J, Iyengar SK, Freedman BI, Kimmel PL, Knowler WC, Kohn OF, Kramp K, Leehey DJ, Nicholas SB, Pahl MV, Schelling JR, Sedor JR, Thornley-Brown D, Winkler CA, Smith MW, Parekh RS (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40(10):1185–1192. doi:10.1038/ng.232 ng.232 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Kojima S, Nara K, Rifkin DB (1993) Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. J Cell Biol 121(2):439–448

    Article  CAS  PubMed  Google Scholar 

  • Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, Friedman D, Briggs W, Dart R, Korbet S, Mokrzycki MH, Kimmel PL, Limou S, Ahuja TS, Berns JS, Fryc J, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Vlahov D, Pollak M, Winkler CA (2011) APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 22(11):2129–2137. doi:10.1681/ASN.2011040388 ASN.2011040388 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kuwabara A, Satoh M, Tomita N, Sasaki T, Kashihara N (2010) Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats. Diabetologia 53(9):2056–2065. doi:10.1007/s00125-010-1810-0

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levey AS, Coresh J (2012) Chronic kidney disease. Lancet 379(9811):165–180. doi:10.1016/S0140-6736(11)60178-5 S0140-6736(11)60178-5 [pii]

    Article  PubMed  Google Scholar 

  • Lin SL, Kisseleva T, Brenner DA, Duffield JS (2008) Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 173(6):1617–1627. doi:10.2353/ajpath.2008.080433 S0002-9440(10)61547-7 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu Y (2004) Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 15(1):1–12

    Article  CAS  PubMed  Google Scholar 

  • Liu Y (2010) New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 21(2):212–222. doi:10.1681/ASN.2008121226 ASN.2008121226 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu S, Li Y, Zhao H, Chen D, Huang Q, Wang S, Zou W, Zhang Y, Li X, Huang H (2006) Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats. Mol Cell Biochem 284(1–2):9–17. doi:10.1007/s11010-005-9005-6

    Article  CAS  PubMed  Google Scholar 

  • Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4(2):140–156. doi:10.1038/nrm1014 nrm1014 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Lortat-Jacob H, Burhan I, Scarpellini A, Thomas A, Imberty A, Vives RR, Johnson T, Gutierrez A, Verderio EA (2012) Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. J Biol Chem. doi:M111.337089 [pii] 10.1074/jbc.M111.337089

  • Maezawa Y, Takemoto M, Yokote K (2015) Cell biology of diabetic nephropathy: roles of endothelial cells, tubulointerstitial cells and podocytes. J Diabetes Investig 6(1):3–15. doi:10.1111/jdi.12255

    Article  PubMed Central  PubMed  Google Scholar 

  • McCarthy KJ, Wassenhove-McCarthy DJ (2012) The glomerular basement membrane as a model system to study the bioactivity of heparan sulfate glycosaminoglycans. Microsc Microanal 18(1):3–21. doi:10.1017/S1431927611012682 S1431927611012682 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mengel M, Bock O, Priess M, Haller H, Kreipe H, Gwinner W (2008) Expression of pro- and antifibrotic genes in protocol biopsies from renal allografts with interstitial fibrosis and tubular atrophy. Clin Nephrol 69(6):408–416

    Article  CAS  PubMed  Google Scholar 

  • Mirza A, Liu SL, Frizell E, Zhu J, Maddukuri S, Martinez J, Davies P, Schwarting R, Norton P, Zern MA (1997) A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-kappaB. Am J Physiol 272(2 Pt 1):G281–G288

    CAS  PubMed  Google Scholar 

  • Moe SM, Chen NX (2008) Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol 19(2):213–216. doi:ASN.2007080854 [pii] 10.1681/ASN.2007080854

    Article  CAS  PubMed  Google Scholar 

  • Moe SM, Drueke T, Lameire N, Eknoyan G (2007) Chronic kidney disease-mineral-bone disorder: a new paradigm. Adv Chronic Kidney Dis 14(1):3–12. doi:S1548-5595(06)00167-4 [pii] 10.1053/j.ackd.2006.10.005

    Article  PubMed  Google Scholar 

  • Moe SM, Chen NX, Seifert MF, Sinders RM, Duan D, Chen X, Liang Y, Radcliff JS, White KE, Gattone VH 2nd (2009) A rat model of chronic kidney disease-mineral bone disorder. Kidney Int 75(2):176–184. doi:10.1038/ki.2008.456 ki2008456 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morita H, Shinzato T, David G, Mizutani A, Habuchi H, Fujita Y, Ito M, Asai J, Maeda K, Kimata K (1994) Basic fibroblast growth factor-binding domain of heparan sulfate in the human glomerulosclerosis and renal tubulointerstitial fibrosis. Lab Invest 71(4):528–535

    CAS  PubMed  Google Scholar 

  • Nadella V, Wang Z, Johnson TS, Griffin M, Devitt A (2015) Transglutaminase 2 interacts with syndecan-4 and CD44 at the surface of human macrophages to promote removal of apoptotic cells. Biochim Biophys Acta 1853(1):201–212. doi:10.1016/j.bbamcr.2014.09.020 S0167-4889(14)00345-0 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T, Li Q (2011) Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nat Rev Nephrol 7(1):36–44. doi:10.1038/nrneph.2010.152 nrneph.2010.152 [pii]

    Article  PubMed Central  PubMed  Google Scholar 

  • Nicholas B, Smethurst P, Verderio E, Jones R, Griffin M (2003) Cross-linking of cellular proteins by tissue transglutaminase during necrotic cell death: a mechanism for maintaining tissue integrity. Biochem J 371(Pt 2):413–422. doi:10.1042/BJ20021949 BJ20021949 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nieuwdorp M, Mooij HL, Kroon J, Atasever B, Spaan JA, Ince C, Holleman F, Diamant M, Heine RJ, Hoekstra JB, Kastelein JJ, Stroes ES, Vink H (2006) Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes 55(4):1127–1132. doi:55/4/1127 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Nunes I, Gleizes PE, Metz CN, Rifkin DB (1997) Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol 136(5):1151–1163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Olsen KC, Sapinoro RE, Kottmann RM, Kulkarni AA, Iismaa SE, Johnson GV, Thatcher TH, Phipps RP, Sime PJ (2011) Transglutaminase 2 and its role in pulmonary fibrosis. Am J Respir Crit Care Med 184(6):699–707. doi:10.1164/rccm.201101-0013OC 201101-0013OC [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Papasotiriou M, Kalliakmani P, Huang L, Gerolymos M, Goumenos DS, Johnson TS (2012) Does treatment with corticosteroids and cyclosporine reduce transglutaminase type 2 expression in the renal tissue of patients with membranous nephropathy? Nephron Clin Pract 121(1–2):c60–c67. doi:10.1159/000341116 000341116 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Parsons AC, Yosipovitch G, Sheehan DJ, Sangueza OP, Greenberg CS, Sane DC (2007) Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol 29(5):433–436. doi:10.1097/DAD.0b013e318156e43f 00000372-200710000-00001 [pii]

    Article  PubMed  Google Scholar 

  • Ponnusamy M, Pang M, Annamaraju PK, Zhang Z, Gong R, Chin YE, Zhuang S (2009) Transglutaminase-1 protects renal epithelial cells from hydrogen peroxide-induced apoptosis through activation of STAT3 and AKT signaling pathways. Am J Physiol Renal Physiol 297(5):F1361–F1370. doi:10.1152/ajprenal.00251.2009 00251.2009 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rienstra H, Katta K, Celie JW, van Goor H, Navis G, van den Born J, Hillebrands JL (2010) Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats. PLoS One 5(2):e9095. doi:10.1371/journal.pone.0009095

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rosen SD, Lemjabbar-Alaoui H (2010) Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate. Expert Opin Ther Targets 14(9):935–949. doi:10.1517/14728222.2010.504718

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sanchez-Lara AC, Elliott J, Syme HM, Brown CA, Haylor JL (2014) Feline chronic kidney disease is associated with upregulation of transglutaminase 2: a collagen cross-linking enzyme. Vet Pathol. doi:0300985814542811 [pii]. 10.1177/0300985814542811

  • Scarpellini A, Germack R, Lortat-Jacob H, Muramatsu T, Billett E, Johnson T, Verderio EA (2009) Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2. J Biol Chem 284(27):18411–18423. doi:10.1074/jbc.M109.012948 M109.012948 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Scarpellini A, Huang L, Burhan I, Schroeder N, Funck M, Johnson TS, Verderio EA (2014) Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis. J Am Soc Nephrol 25(5):1013–1027. doi:10.1681/ASN.2013050563 ASN.2013050563 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schittny JC, Paulsson M, Vallan C, Burri PH, Kedei N, Aeschlimann D (1997) Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development. Am J Respir Cell Mol Biol 17(3):334–343. doi:10.1165/ajrcmb.17.3.2737

    Article  CAS  PubMed  Google Scholar 

  • Schuksz M, Fuster MM, Brown JR, Crawford BE, Ditto DP, Lawrence R, Glass CA, Wang L, Tor Y, Esko JD (2008) Surfen, a small molecule antagonist of heparan sulfate. Proc Natl Acad Sci U S A 105(35):13075–13080. doi:10.1073/pnas.0805862105 0805862105 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sharma K (2014) Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl (2011) 4(1):113–117. doi:10.1038/kisup.2014.21

  • Shrestha B, Haylor J (2014) Experimental rat models of chronic allograft nephropathy: a review. Int J Nephrol Renov Dis 7:315–322. doi:10.2147/IJNRD.S65604 ijnrd-7-315 [pii]

    Article  Google Scholar 

  • Shrestha B, Butt I, Da Silva M, Sanchez-Lara A, Wagner B, Raftery A, Johnson T, Haylor J (2014) Upregulation of transglutaminase and epsilon (gamma-glutamyl)-lysine in the Fisher-Lewis rat model of chronic allograft nephropathy. Biomed Res Int 2014:651608. doi:10.1155/2014/651608

    PubMed Central  PubMed  Google Scholar 

  • Shweke N, Boulos N, Jouanneau C, Vandermeersch S, Melino G, Dussaule JC, Chatziantoniou C, Ronco P, Boffa JJ (2008) Tissue transglutaminase contributes to interstitial renal fibrosis by favoring accumulation of fibrillar collagen through TGF-beta activation and cell infiltration. Am J Pathol 173(3):631–642. doi:S0002-9440(10)61637-9 [pii] 10.2353/ajpath.2008.080025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Skill NJ, Griffin M, El Nahas AM, Sanai T, Haylor JL, Fisher M, Jamie MF, Mould NN, Johnson TS (2001) Increases in renal epsilon-(gamma-glutamyl)-lysine crosslinks result from compartment-specific changes in tissue transglutaminase in early experimental diabetic nephropathy: pathologic implications. Lab Invest 81(5):705–716

    Article  CAS  PubMed  Google Scholar 

  • Skill NJ, Johnson TS, Coutts IG, Saint RE, Fisher M, Huang L, El Nahas AM, Collighan RJ, Griffin M (2004) Inhibition of transglutaminase activity reduces extracellular matrix accumulation induced by high glucose levels in proximal tubular epithelial cells. J Biol Chem 279(46):47754–47762. doi:10.1074/jbc.M402698200 M402698200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Small K, Feng JF, Lorenz J, Donnelly ET, Yu A, Im MJ, Dorn GW 2nd, Liggett SB (1999) Cardiac specific overexpression of transglutaminase II (G(h)) results in a unique hypertrophy phenotype independent of phospholipase C activation. J Biol Chem 274(30):21291–21296

    Article  CAS  PubMed  Google Scholar 

  • Smethurst PA, Griffin M (1996) Measurement of tissue transglutaminase activity in a permeabilized cell system: its regulation by Ca2+ and nucleotides. Biochem J 313(Pt 3):803–808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG (1995) Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 130(2):393–405

    Article  CAS  PubMed  Google Scholar 

  • Takahashi KMT, Onouchi T, Akiyama S, Hall SD, Tatsukawa H, Kusaka M, Tsutsumi Y, Nagamatsu T, Maruyama S, Kitamura H, Novak J, Hitomi K, Yuzawa Y (2014) Mesangial tissue transglutaminase activity in patients with IgA nephropathy: implications for the pathogenesis. J Am Soc Nephrol 25:909

    Google Scholar 

  • Teesalu K, Panarina M, Uibo O, Uibo R, Utt M (2012) Autoantibodies from patients with celiac disease inhibit transglutaminase 2 binding to heparin/heparan sulfate and interfere with intestinal epithelial cell adhesion. Amino Acids 42(2–3):1055–1064. doi:10.1007/s00726-011-1020-1

    Article  CAS  PubMed  Google Scholar 

  • Telci D, Wang Z, Li X, Verderio EA, Humphries MJ, Baccarini M, Basaga H, Griffin M (2008) Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta1 integrin co-signaling. J Biol Chem 283(30):20937–20947. doi:10.1074/jbc.M801763200. doi:M801763200 [pii] 10.1074/jbc.M801763200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Verderio E, Scarpellini A (2010) Significance of the syndecan-4-transglutaminase-2 interaction. ScientificWorldJournal 10:1073–1077. doi:10.1100/tsw.2010.102

    Article  CAS  PubMed  Google Scholar 

  • Verderio E, Nicholas B, Gross S, Griffin M (1998) Regulated expression of tissue transglutaminase in Swiss 3T3 fibroblasts: effects on the processing of fibronectin, cell attachment, and cell death. Exp Cell Res 239(1):119–138. doi:S0014-4827(97)93874-X [pii] 10.1006/excr.1997.3874

    Article  CAS  PubMed  Google Scholar 

  • Verderio E, Gaudry C, Gross S, Smith C, Downes S, Griffin M (1999) Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1. J Histochem Cytochem 47(11):1417–1432

    Article  CAS  PubMed  Google Scholar 

  • Verderio EA, Telci D, Okoye A, Melino G, Griffin M (2003) A novel RGD-independent cel adhesion pathway mediated by fibronectin-bound tissue transglutaminase rescues cells from anoikis. J Biol Chem 278(43):42604–42614. doi:10.1074/jbc.M303303200 M303303200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Verderio EA, Scarpellini A, Johnson TS (2009) Novel interactions of TG2 with heparan sulfate proteoglycans: reflection on physiological implications. Amino Acids 36(4):671–677. doi:10.1007/s00726-008-0134-6

    Article  CAS  PubMed  Google Scholar 

  • Vielhauer V, Anders HJ, Mack M, Cihak J, Strutz F, Stangassinger M, Luckow B, Grone HJ, Schlondorff D (2001) Obstructive nephropathy in the mouse: progressive fibrosis correlates with tubulointerstitial chemokine expression and accumulation of CC chemokine receptor 2- and 5-positive leukocytes. J Am Soc Nephrol 12(6):1173–1187

    CAS  PubMed  Google Scholar 

  • Wang Z, Griffin M (2012) TG2, a novel extracellular protein with multiple functions. Amino Acids 42(2–3):939–949. doi:10.1007/s00726-011-1008-x

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Telci D, Griffin M (2011) Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex. Exp Cell Res 317(3):367–381. doi:10.1016/j.yexcr.2010.10.015 S0014-4827(10)00481-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Collighan RJ, Pytel K, Rathbone DL, Li X, Griffin M (2012) Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling. J Biol Chem 287(16):13063–13083. doi:10.1074/jbc.M111.294819 M111.294819 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yung S, Woods A, Chan TM, Davies M, Williams JD, Couchman JR (2001) Syndecan-4 up-regulation in proliferative renal disease is related to microfilament organization. FASEB J 15(9):1631–1633

    CAS  PubMed  Google Scholar 

  • Zehe C, Engling A, Wegehingel S, Schafer T, Nickel W (2006) Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proc Natl Acad Sci U S A 103(42):15479–15484. doi:0605997103 [pii] 10.1073/pnas.0605997103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R (2008) Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol 19(12):2282–2287. doi:10.1681/ASN.2008050513 ASN.2008050513 [pii]

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhang Z, Xing J, Ma L, Gong R, Chin YE, Zhuang S (2009) Transglutaminase-1 regulates renal epithelial cell proliferation through activation of Stat-3. J Biol Chem 284(5):3345–3353. doi:10.1074/jbc.M808396200 M808396200 [pii]

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao G, Zhang ZQ, Zhang B, Luo M, Sun YW, Wu ZY (2011) Down-regulation of tTG expression by RNAi inhibits HSC proliferation and attenuates liver fibrosis. Int J Clin Exp Pathol 4(5):513–520

    PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Kidney Research UK RP25/2012, the Wellcome Trust [087163], Nottingham Trent University and Sheffield Kidney Research Foundation for supporting our work.

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Authors and Affiliations

  1. Biomedical Life and Health Science Research Centre, School of Science & Technology, Nottingham Trent University, Nottingham, UK

    Elisabetta A. M. Verderio, Giulia Furini & Izhar W. Burhan

  2. Academic Nephrology Unit, Sheffield Kidney Institute, University of Sheffield, Sheffield, UK

    Timothy S. Johnson

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  1. Elisabetta A. M. Verderio
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  2. Giulia Furini
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  3. Izhar W. Burhan
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  4. Timothy S. Johnson
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Correspondence to Elisabetta A. M. Verderio or Timothy S. Johnson .

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Editors and Affiliations

  1. Grad Sch of Pharmaceutical Sciences, Nagoya University, Nagoya, Aichi, Japan

    Kiyotaka Hitomi

  2. Micro-Signaling Regulation Technol. Unit, RIKEN Center for Life Sci. Technologies, Wako, Saitama, Japan

    Soichi Kojima

  3. Dept. Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary

    Laszlo Fesus

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Verderio, E.A.M., Furini, G., Burhan, I.W., Johnson, T.S. (2015). Transglutaminases: Expression in Kidney and Relation to Kidney Fibrosis. In: Hitomi, K., Kojima, S., Fesus, L. (eds) Transglutaminases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55825-5_11

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