Interaction of uromodulin and complement factor H enhances C3b inactivation.

Interaction of uromodulin and complement factor H enhances C3b inactivation.
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尿调节素和补体因子 H 的相互作用增强 C3b 失活

DOI:
10.1111/jcmm.12872
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发表时间:
2016-10
影响因子:
5.3
通讯作者:
Zhao MH
Zhao MH
中科院分区:
医学2区
文献类型:
--
作者:
Liu M;Wang Y;Wang F;Xia M;Liu Y;Chen Y;Zhao MH

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最近的研究表明,尿调素在慢性肾脏疾病中起着重要作用。它可以与几种补体成分,各种细胞因子和免疫系统细胞相互作用。补体因子H(CFH)作为补体旁路途径的调节因子,也与各种肾脏疾病相关。因此,我们已经表明,尿调节素调节补体激活与CFH相互作用在肾小管间质损伤。我们通过免疫荧光检测尿调素和CFH在肾小管中的共定位。接下来,我们在体外证实了尿调节素与CFH的结合,并且基于表面等离子体共振结果发现尿调节素与CFH结合的亲和常数(KD)为4.07 × 10− 6 M。CFH上的结合位点被定义为短共有重复(SCR)单元SCR 1 -4、SCR 7和SCR 19 -20。尿调蛋白-CFH相互作用增强了CFH的辅因子活性,使I因子介导的C3 b裂解为iC 3b。这些结果表明,尿调素通过结合和增强CFH的功能发挥作用。
Recent studies suggest that uromodulin plays an important role in chronic kidney diseases. It can interact with several complement components, various cytokines and immune system cells. Complement factor H (CFH), as a regulator of the complement alternative pathway, is also associated with various renal diseases. Thus, we have been suggested that uromodulin regulates complement activation by interacting with CFH during tubulointerstitial injury. We detected co‐localization of uromodulin and CFH in the renal tubules by using immunofluorescence. Next, we confirmed the binding of uromodulin with CFH in vitro and found that the affinity constant (KD) of uromodulin binding to CFH was 4.07 × 10−6M based on surface plasmon resonance results. The binding sites on CFH were defined as the short consensus repeat (SCR) units SCR1–4, SCR7 and SCR19–20. The uromodulin‐CFH interaction enhanced the cofactor activity of CFH for factor I‐mediated cleavage of C3b to iC3b. These results indicate that uromodulin plays a role via binding and enhancing the function of CFH.
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