Renal expression of alpha-smooth muscle actin and c-Met in children with Henoch–Schönlein purpura nephritis

Abstract

Alpha-smooth muscle actin (α-SMA) is the actin isoform that predominates within vascular smooth-muscle cells and plays an important role in fibrogenesis. On the other hand, c-Met is the receptor for hepatocyte growth factor (HGF), which plays a role in protection from injury and has anti-fibrogenetic effects. To clarify whether α-SMA and HGF are associated with the progression of renal injury in Henoch–Schönlein purpura nephritis (HSPN), we evaluated the renal expression of α-SMA and c-Met in HSPN patients. Patients were divided into three groups. Group 1 consisted of eight patients (male:female 4:4) with stage II or less in the classification of the International Study of Kidney Disease in Children (ISKDC), Group 2 consisted of 20 patients (male:female 11:9) with ISKDC stage III or greater and a good prognosis, and group 3 consisted of seven patients (male:female 3:4) with ISKDC stage III or greater and poor prognosis. Renal biopsy findings, including c-Met and α-SMA staining, were investigated for each group. At first biopsy, the mean scores for renal α-SMA and glomerular c-Met in groups 2 and 3 were higher than those in group 1, while mean scores for neither renal α-SMA nor glomerular c-Met differed between groups 2 and 3. At second biopsy, the mean scores for renal α-SMA staining in group 3 were higher than those in group 2, and mean score for glomerular c-Met staining in group 3 was lower than that in group 2. In groups 2 and 3, the mean scores for glomerular and interstitial α-SMA staining at first biopsy were correlated with the chronicity index (CI) at second biopsy, but the mean score for glomerular c-Met staining at first biopsy correlated with neither the activity index (AI) nor CI in the first or second biopsies in all groups. Our findings suggest that the expression of renal α-SMA may be associated with progression of renal injury in HSPN.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Habib R, Niaudet R, Levy M (1994) Schoenlein-Henoch purpura nephritis and IgA nephropathy. In: Tisher CC, Brenner BM (eds) Renal pathology with clinical and functional correlations, 2nd edn. Lippincott, Philadelphia, pp 427–523

    Google Scholar 

  2. 2.

    Counahan R, Winterborn MH, White RHR (1977) Prognosis of Henoch–Schönlein nephritis in children. Br Med J 2:11–14

    CAS  Article  Google Scholar 

  3. 3.

    Haycock GB (1998) The nephritis of Henoch–Schönlein purpura. In: Cameron JS (ed) Oxford textbook of nephrology, 2nd edn. Oxford University Press, Oxford, pp 585–612

    Google Scholar 

  4. 4.

    Coppo R, Mazzucco G, Cagnoli L, Lupo A, Schena P, Italian Group of Renal Immunopathology Collaborative Study on Henoch–Schonlein Purpura (1997) Long-term prognosis of Henoch–Schonlein nephritis in adults and children. Nephrol Dial Transplant 12:2277–2283

    CAS  Article  Google Scholar 

  5. 5.

    Sappino AP, Schurch W, Gabbiani G (1990) Differentiation repertoire of fibroblastic cells; expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63:144–161

    CAS  PubMed  Google Scholar 

  6. 6.

    Alpers CE, Hudkins KL, Gown AM, Johnson RJ (1992) Enhanced expression of ‘muscle-specific’ actin in glomerulonephritis. Kidney Int 41:1134–1142

    CAS  Article  Google Scholar 

  7. 7.

    Nakamura T, Nishizawa T, Hagiya M, Seki T, Schimonishi M, Sugimura A, Tashiro K, Shimizu S (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342:440–443

    CAS  Article  Google Scholar 

  8. 8.

    Matsumoto K, Nakamura T (2001) Hepatocyte growth factor: renotropic role and potential therapeutics for renal disease. Kidney Int 59:2023–2038

    CAS  Article  Google Scholar 

  9. 9.

    Kawaida K, Natsumoto K, Shimazu H, Nakamura T (1994) Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. Proc Nati Acad Sci U S A 91:4357–4361

    CAS  Article  Google Scholar 

  10. 10.

    Miller SB, Martin DR, Kissane J, Hammeman MR (1994) Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats. Am J Physiol 266:F129–F134

    PubMed  Google Scholar 

  11. 11.

    Liu Y, Wikinson FL, Kirton JP, Jeziorska M, Lizasa H, Sai Y, Nakashima E, Heagerty AM, Canfield AE, Alexander MY (2007) Hepatocyte growth factor and c-Met expression in pericytes: implications for atherosclerotic plaque development. J Pathol 212:12–19

    CAS  Article  Google Scholar 

  12. 12.

    Meadow SR, Glasgow EF, White RHR (1972) Schönlein-Henoch nephritis. Q J Med 41:241–258

    CAS  Google Scholar 

  13. 13.

    White RHR (1994) Henoch-Schönlein nephritis. A disease with significant late sequelae. Nephron 68:1–9

    CAS  Article  Google Scholar 

  14. 14.

    Zhang G, Moorhead PJ, El Nahas AM (1995) Myofibroblasts and the progression of experimental glomerulonephritis. Kidney Int 3:308–318

    CAS  Google Scholar 

  15. 15.

    Goumenous D, Brown CB, Shortland J, El Nahas AM (1994) Myofibroblasts and the progression of mesangial IgA nephropathy. Nephrol Dial Transplant 9:1418–1425

    Google Scholar 

  16. 16.

    Goumenos D, Tsomi K, Iatrou C, Oldroyd S, Sungur A, Papaioannides D, Moustakas G, Ziroyannis P, Mountokalakis T, El Nahas AM (1998) Myofibroblasts and the progression of crescentic glomerulonephritis. Nephrol Dial Transplant 13:1652–1661

    CAS  Article  Google Scholar 

  17. 17.

    Utsunomiya Y, Kawamura T, Abe A, Imai H, Hirano K, Maruyama N, Hosoya T, Sakai O (1999) Significance of mesangial expression of α-smooth muscle actin in the progression of IgA nephropathy. Am J Kidney Dis 34:902–910

    CAS  Article  Google Scholar 

  18. 18.

    Kawasaki Y, Suzuki J, Sakai N, Tanji M, Suzuki H (2003) Predicting the prognosis of renal dysfunction by renal expression of α-smooth muscle actin in children with MPGN type 1. Am J Kidney Dis 42:1131–1138

    CAS  Article  Google Scholar 

  19. 19.

    Cantley LG, Barros EJG, Gandhi M, Rauchman M, Nigam SK (1994) Regulation of mitogenesis, motogenesis, and tubulogenesis by hepatocyte growth factor in renal collecting duct cells. Am J Physiol 267:F271–F280

    CAS  PubMed  Google Scholar 

  20. 20.

    Rampino T, Gregorini M, Camussi G, Conaldi PG, Soccio G, Maggio M, Bottelli A, Canton AD (2005) Hepatocyte growth factor and its receptor Met are induced in crescentic glomerulonephritis. Nephrol Dial Transplant 20:1066–1074

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yukihiko Kawasaki.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kawasaki, Y., Imaizumi, T., Matsuura, H. et al. Renal expression of alpha-smooth muscle actin and c-Met in children with Henoch–Schönlein purpura nephritis. Pediatr Nephrol 23, 913–919 (2008). https://doi.org/10.1007/s00467-008-0749-6

Download citation

Keywords

  • HGF
  • α-SMA
  • c-Met
  • HSPN
  • Prognosis