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Genes & Genomics

, Volume 41, Issue 4, pp 397–406 | Cite as

C1q and TNF related protein 1 regulates expression of inflammatory genes in vascular smooth muscle cells

  • Dough Kim
  • Seung-Yoon ParkEmail author
Research Article
  • 65 Downloads

Abstract

Background

C1q and TNF related protein 1 (C1QTNF1) is known to be associated with coronary artery diseases. However, the molecular function of C1QTNF1 on the vascular smooth muscles remains to be investigated.

Objective

This study was therefore undertaken to investigate the effect of C1QTNF1 on gene expression of human smooth muscle cells and to reveal potential molecular mechanisms mediated by C1QTNF1.

Methods

Vascular smooth muscle cells were incubated with recombinant C1QTNF1 for 16 h, followed by determining any change in mRNA expressions by Affymetrix genechip. Gene ontology (GO), KEGG pathway, and protein–protein interaction (PPI) network were analyzed in differentially expressed genes. In addition, validation of microarray data was performed using quantitative real-time PCR.

Results

The mRNA expressions of annotated 74 genes were significantly altered after incubation with recombinant C1QTNF1; 41 genes were up-regulated and 33 down-regulated. The differentially expressed genes were enriched in biological processes and KEGG pathways associated with inflammatory responses. In the PPI network analysis, IL-6, CCL2, and ICAM1 were identified as potential key genes with relatively high degree. The cluster analysis in the PPI network identified a significant module composed of upregulated genes, such as IL-6, CCL2, NFKBIA, SOD2, and ICAM1. The quantitative real-time PCR results of potential key genes were consistent with microarray data.

Conclusion

The results in the present study provide insights on the effects of C1QTNF1 on gene expression of smooth muscle cells. We believe our findings will help to elucidate the molecular mechanisms regarding the functions of C1QTNF1 on smooth muscle cells in inflammatory diseases.

Keywords

CTRP1 C1QTNF1 Gene expression Regulation Microarray 

Notes

Author contributions

Conceptualization: S-YP. Methodology: DK, S-YP. Formal analysis: DK, S-YP. Data curation: DK, S-YP. Investigation: DK, S-YP. Writing-original draft: S-YP. Wright-review and editing: S-YP. Approval of final manuscript: all authors.

Funding

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2017R1A2B4002662).

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest to disclose.

Supplementary material

13258_2018_770_MOESM1_ESM.xls (38 kb)
Supplementary material 1 (XLS 38 KB)
13258_2018_770_MOESM2_ESM.pdf (127 kb)
Supplementary material 2 (PDF 127 KB)

References

  1. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Natoli E, Rollins BJ, Milos PM (1999) Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 19:1518–1525CrossRefGoogle Scholar
  2. Akiyama H, Otani M, Sato S, Toyosawa S, Furukawa S, Wakisaka S, Maeda T (2013) A novel adipokine C1q/TNF-related protein 1 (CTRP1) regulates chondrocyte proliferation and maturation through the ERK1/2 signaling pathway. Mol Cell Endocrinol 369:63–71.  https://doi.org/10.1016/j.mce.2013.01.002 CrossRefGoogle Scholar
  3. Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87:13–20CrossRefGoogle Scholar
  4. Braun M, Pietsch P, Schror K, Baumann G, Felix SB (1999) Cellular adhesion molecules on vascular smooth muscle cells. Cardiovasc Res 41:395–401CrossRefGoogle Scholar
  5. Cheng X, Wang Y, Chen H, Xu Y, Xiong W, Wang T (2017) Claudin-1 regulates pulmonary artery smooth muscle cell proliferation through the activation of ERK1/2. Biomed Pharmacother 89:983–990.  https://doi.org/10.1016/j.biopha.2017.02.063 CrossRefGoogle Scholar
  6. Falk E (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47:C7–C12.  https://doi.org/10.1016/j.jacc.2005.09.068 CrossRefGoogle Scholar
  7. Ikeda U, Ikeda M, Seino Y, Takahashi M, Kano S, Shimada K (1992) Interleukin 6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. Atherosclerosis 92:213–218CrossRefGoogle Scholar
  8. Inoue S et al (2002) Anti-monocyte chemoattractant protein-1 gene therapy limits progression and destabilization of established atherosclerosis in apolipoprotein E-knockout mice. Circulation 106:2700–2706CrossRefGoogle Scholar
  9. Jeon JH et al (2008) A novel adipokine CTRP1 stimulates aldosterone production. FASEB J 22:1502–1511.  https://doi.org/10.1096/fj.07-9412com CrossRefGoogle Scholar
  10. Kanemura N et al (2017) C1q/TNF-related protein 1 prevents neointimal formation after arterial injury. Atherosclerosis 257:138–145.  https://doi.org/10.1016/j.atherosclerosis.2017.01.014 CrossRefGoogle Scholar
  11. Lasser G et al (2006) C1qTNF-related protein-1 (CTRP-1): a vascular wall protein that inhibits collagen-induced platelet aggregation by blocking VWF binding to collagen. Blood 107:423–430.  https://doi.org/10.1182/blood-2005-04-1425 CrossRefGoogle Scholar
  12. Lee GL, Chang YW, Wu JY, Wu ML, Wu KK, Yet SF, Kuo CC (2012) TLR 2 induces vascular smooth muscle cell migration through cAMP response element-binding protein-mediated interleukin-6 production. Arterioscler Thromb Vasc Biol 32:2751–2760.  https://doi.org/10.1161/ATVBAHA.112.300302 CrossRefGoogle Scholar
  13. Liu ZH et al (2017) C1q/TNF-related protein 1 promotes endothelial barrier dysfunction under disturbed flow. Biochem Biophys Res Commun 490:580–586.  https://doi.org/10.1016/j.bbrc.2017.06.081 CrossRefGoogle Scholar
  14. Lu L et al (2016) C1q/TNF-related protein-1: an adipokine marking and promoting atherosclerosis. Eur Heart J 37:1762–1771.  https://doi.org/10.1093/eurheartj/ehv649 CrossRefGoogle Scholar
  15. Luo JL, Kamata H, Karin M (2005) The anti-death machinery in IKK/NF-kappaB signaling. J Clin Immunol 25:541–550.  https://doi.org/10.1007/s10875-005-8217-6 CrossRefGoogle Scholar
  16. Morimoto S et al (1991) Interleukin-6 stimulates proliferation of cultured vascular smooth muscle cells independently of interleukin-1 beta. J Cardiovasc Pharmacol 17(Suppl 2):S117–S118CrossRefGoogle Scholar
  17. Ni W et al (2001) New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 103:2096–2101CrossRefGoogle Scholar
  18. Park SY, Choi GH, Choi HI, Ryu J, Jung CY, Lee W (2005) Depletion of mitochondrial DNA causes impaired glucose utilization and insulin resistance in L6 GLUT4myc myocytes. J Biol Chem 280:9855–9864CrossRefGoogle Scholar
  19. Patel VI et al (2006) A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and induces regression of neointimal hyperplasia. FASEB J 20:1418–1430.  https://doi.org/10.1096/fj.05-4981com CrossRefGoogle Scholar
  20. Peterson JM, Aja S, Wei Z, Wong GW (2012) CTRP1 protein enhances fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase (ACC) inhibition. J Biol Chem 287:1576–1587.  https://doi.org/10.1074/jbc.M111.278333 CrossRefGoogle Scholar
  21. Raines EW, Ferri N (2005) Thematic review series: the immune system and atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular disease. J Lipid Res 46:1081–1092.  https://doi.org/10.1194/jlr.R500004-JLR200 CrossRefGoogle Scholar
  22. Reape TJ, Groot PH (1999) Chemokines and atherosclerosis. Atherosclerosis 147:213–225CrossRefGoogle Scholar
  23. Rollins BJ (1991) JE/MCP-1: an early-response gene encodes a monocyte-specific cytokine. Cancer Cells 3:517–524Google Scholar
  24. Rong JX, Shapiro M, Trogan E, Fisher EA (2003) Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci USA 100:13531–13536.  https://doi.org/10.1073/pnas.1735526100 CrossRefGoogle Scholar
  25. Shannon P et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504.  https://doi.org/10.1101/gr.1239303 CrossRefGoogle Scholar
  26. Szklarczyk D et al (2015) STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acid Res 43:D447-452  https://doi.org/10.1093/nar/gku1003 CrossRefGoogle Scholar
  27. Tang JN et al (2015) Plasma levels of C1q/TNF-related protein 1 and interleukin 6 in patients with acute coronary syndrome or stable angina pectoris. Am J Med Sci 349:130–136.  https://doi.org/10.1097/MAJ.0000000000000378 CrossRefGoogle Scholar
  28. Tatara Y et al (2009) Macrophage inflammatory protein-1β induced cell adhesion with increased intracellular reactive oxygen species. J Mol Cell Cardiol 47:104–111.  https://doi.org/10.1016/j.yjmcc.2009.03.012 CrossRefGoogle Scholar
  29. Wang X, Feuerstein GZ, Clark RK, Yue TL (1994) Enhanced leucocyte adhesion to interleukin-1β stimulated vascular smooth muscle cells is mainly through intercellular adhesion molecule-1. Cardiovasc Res 28:1808–1814CrossRefGoogle Scholar
  30. Wang H et al (2007) Inhibition of terminal complement components in presensitized transplant recipients prevents antibody-mediated rejection leading to long-term graft survival and accommodation. J Immunol 179:4451–4463CrossRefGoogle Scholar
  31. Wang H, Wang R, Du D, Li F, Li Y (2016a) Serum levels of C1q/TNF-related protein-1 (CTRP-1) are closely associated with coronary artery disease. BMC Cardiovasc Disord 16:92.  https://doi.org/10.1186/s12872-016-0266-7 CrossRefGoogle Scholar
  32. Wang XQ et al (2016b) C1q/TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis. Atherosclerosis 250:38–45.  https://doi.org/10.1016/j.atherosclerosis.2016.04.024 CrossRefGoogle Scholar
  33. Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF (2008) Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J 416:161–177.  https://doi.org/10.1042/BJ20081240 CrossRefGoogle Scholar
  34. Yuasa D et al (2014) Association of circulating C1q/TNF-related protein 1 levels with coronary artery disease in men. PLoS ONE 9:e99846.  https://doi.org/10.1371/journal.pone.0099846 CrossRefGoogle Scholar
  35. Yuasa D et al (2016) C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart. FASEB J 30:1065–1075.  https://doi.org/10.1096/fj.15-279885 CrossRefGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biochemistry, School of MedicineDongguk UniversityGyeongjuRepublic of Korea

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