Uromodulin aggravates renal tubulointerstitial injury through activation of the complement pathway in rats,Journal of Cellular Physiology

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Uromodulin aggravates renal tubulointerstitial injury through activation of the complement pathway in rats
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-01-05 , DOI: 10.1002/jcp.30208
Li Yu ₁ , Fei Pei ₂ , Qiaoling Sun ₂ , Fei Shen ₂ , Xiangdong Yang ₂ , Zhao Hu ₂ , Maojing Liu ₂

Affiliation

Uromodulin (Umod) is the most abundant constituent of urine in humans and exclusively found in the kidney tubular epithelium. However, the specific role of Umod in renal tubulointerstitial injury is yet to be understood. The present study was conducted with aim of investigating the potential therapeutic mechanism of Umod in the regulation of renal tubulointerstitial injury. Protein expression of Umod in renal tubular epithelial cells was measured with the conduction of Western blot analysis. Enzyme‐linked immunosorbent assay and immunofluorescence assay were performed to detect the complement activation products and the activation products of surface deposition. The expression of C1q, C2, C4, B factor, C3, C5, H factor, CD46, CD55, C3aR, and C5aR were determined with the use of reverse‐transcription quantitative polymerase chain reaction and Western blot analyses. Subsequently, the unilateral ureteral obstruction (UUO) rat model was established. Renal tubulointerstitial injury was assessed with the application of hematoxylin–eosin staining and Masson staining in rats. UUO rats and normal rats were injected with si‐NC or si‐Umod and complement inhibitor. UUO rats were observed to have serious impairment of kidney tubule, renal tubular dilation, and epithelial atrophy, with downregulated Umod and activated complement pathway. Silencing of Umod resulted in the activation of complement system while promoting interstitial fibrosis in renal tubules. Moreover, addition of complement inhibitor significantly alleviated the renal tubule injury and fibrosis. Collectively, our study suggests that silencing of Umod mediates the complement pathway, exacerbating renal tubulointerstitial injury in rats, which provides insight into the development of novel therapeutic agents for renal tubulointerstitial injury.

中文翻译：

尿调制素通过激活补体通路加重大鼠肾小管间质损伤

尿调制素 (Umod) 是人体尿液中含量最丰富的成分，仅存在于肾小管上皮中。然而，Umod 在肾小管间质损伤中的具体作用尚不清楚。本研究旨在探讨 Umod 在调节肾小管间质损伤中的潜在治疗机制。肾小管上皮细胞中Umod的蛋白表达通过Western印迹分析的传导进行测量。用酶联免疫吸附法和免疫荧光法检测补体激活产物和表面沉积激活产物。C1q、C2、C4、B因子、C3、C5、H因子、CD46、CD55、C3aR、使用逆转录定量聚合酶链反应和蛋白质印迹分析确定 C5aR 和 C5aR。随后，建立单侧输尿管梗阻（UUO）大鼠模型。通过在大鼠中应用苏木精-伊红染色和马森染色评估肾小管间质损伤。UUO 大鼠和正常大鼠注射 si-NC 或 si-Umod 和补体抑制剂。观察到UUO大鼠肾小管严重受损，肾小管扩张和上皮萎缩，Umod下调，补体通路激活。Umod 的沉默导致补体系统的激活，同时促进肾小管的间质纤维化。此外，补体抑制剂的加入显着减轻了肾小管损伤和纤维化。集体，

更新日期：2021-01-05

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