Background/Purpose: As a novel proinflammatory and potential profibrotic factor, the role of CYR61 on the vascular fibrosis of Takayasu arteritis (TA) has not been investigated.

Methods: CYR61 expression was analysed in aortic vessel samples from TA patients and healthy donors by immunohistochemistry tests. The in vitro effect of recombinant human CYR61 (rhCYR61) on the proliferation, migration and activity of adventitial fibroblasts (AFs) in the inflammatory microenvironment was studied.

Results: CYR61 showed obviously higher expression in the TA-affected vessel wall. The proliferation of AFs and the synthesis of ECM components such as collagen I, collagen III and fibronectin were stimulated by rhCYR61. rhCYR61 also partly blocked the migration of AFs. The integrin αvβ1 was identified as the membrane receptor of CYR61, and phosphorylation of the Erk1/2 pathway was also identified. Pretreatment with PD98059, an inhibitor of Erk1/2, resulted in a remarkable decline in the mRNA and protein expression of collagens and fibronectin. Furthermore, rhCYR61 upregulated the expression of TGF-β in AFs, and TGF-β siRNA transfection obviously attenuated the profibrotic effect of rhCYR61. Finnally, recombinant human IL-17 (rhIL-17) could promote the expression of CYR61 in AFs, and the combination of rhIL-17 and rhCYR61 dramatically strengthened the synthesis of ECM. The CYR61 monoclonal antibody diminished these effects of rhIL-17 in AFs.

Conclusion: These findings indicated that CYR61/Erk1/2/TGF-β pathway played a profibrotic role in the pathogenesis of TA, and this was enhanced by IL-17 mediated inflammatory environment. Thus, targeting CYR61 may have potential clinical values in the future.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cyr61-tgf-%ce%b2-axis-promotes-adventitial-fibrosis-of-takayasu-arteritis-in-the-il-17-mediated-inflammatory-microenvironment/