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中华肾病研究电子杂志 ›› 2023, Vol. 12 ›› Issue (04) : 224 -228. doi: 10.3877/cma.j.issn.2095-3216.2023.04.009

综述

通过抑制Wnt/β-catenin信号通路延缓肾间质纤维化研究进展
李思佳, 苏晓乐(), 王利华   
  1. 030001 太原,山西医科大学第二医院肾内科、山西省肾脏病研究所
  • 收稿日期:2022-07-18 出版日期:2023-08-28
  • 通信作者: 苏晓乐
  • 基金资助:
    国家自然科学基金(82000655); 山西省卫生健康委科研课题(2022002)

Progress of research on inhibition of Wnt/β-catenin signaling pathway to delay renal interstitial fibrosis

Sijia Li, Xiaole Su(), Lihua Wang   

  1. Department of Nephrology, Second Hospital Affiliated to Shanxi Medical University, Shanxi Provincial Kidney Disease Institute, Taiyuan 030001, China
  • Received:2022-07-18 Published:2023-08-28
  • Corresponding author: Xiaole Su
引用本文:

李思佳, 苏晓乐, 王利华. 通过抑制Wnt/β-catenin信号通路延缓肾间质纤维化研究进展[J]. 中华肾病研究电子杂志, 2023, 12(04): 224-228.

Sijia Li, Xiaole Su, Lihua Wang. Progress of research on inhibition of Wnt/β-catenin signaling pathway to delay renal interstitial fibrosis[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(04): 224-228.

肾间质纤维化是慢性肾脏病进展的重要病理基础,延缓肾间质纤维化的过程可抑制慢性肾脏病发展。在肾间质纤维化动物模型中,使用Wnt抑制剂,可干预Wnt/β-catenin信号通路及其下游靶基因信号传导、肾小管上皮间充质转化(EMT),从而延缓肾间质纤维化进程。Wnt/β-catenin信号通路及其下游靶基因都可能是该通路的调节点,成为延缓肾间质纤维化的潜在目标。本文对通过抑制Wnt/β-catenin信号通路延缓肾间质纤维化的研究进展进行综述。

Renal interstitial fibrosis is an important pathological basis for the progression of chronic kidney disease. Delaying the process of renal interstitial fibrosis may inhibit the progression of chronic kidney disease. In animal models of renal interstitial fibrosis, the use of Wnt inhibitors could interfere with signal transduction of Wnt/β-catenin signaling pathway and its downstream target genes as well as renal tubular epithelial-mesenchymal transition (EMT), thereby delaying the progression of renal interstitial fibrosis. The Wnt/β-catenin signaling pathway and its downstream target genes may all be the potential regulatory molecules, becoming the potential targets to delay renal interstitial fibrosis. This article reviewed the research progress on inhibition of Wnt/β-catenin signaling pathway to delay renal interstitial fibrosis.

图1 Wnt/β-catenin通路的活化与肾间质纤维化注:A:Wnt抑制剂阻断Wnt/β-catenin信号通路,抑制肾间质纤维化。Wnt抑制剂抑制Wnt与FZD受体结合,阻断了Wnt信号,磷酸化的β-catenin与Axin/APC/GSK-3β/CKI形成复合物维持细胞正常形态。Wnt/β-catenin信号通路被阻断,肾间质纤维化发生被抑制;B:Wnt/β-catenin通路活化参与肾间质纤维化发生。FZD受体与Wnt结合,使β-catenin从Axin/APC/GSK-3β/CKI复合物上脱落下来,进入细胞核内与T细胞因子(TCF)和淋巴增强因子(LEF)结合,驱动下游纤维化靶基因转录,促进肾间质纤维化发生。sFRP:分泌型FZD相关蛋白;AOPPs:高级氧化蛋白产物;SIK1:盐诱导激酶1; DOCK4:胞质分裂作用因子4; USP36:泛素特异性蛋白酶36; Axin: Axis抑制蛋白;CK1:casein kinase 1,1型酪蛋白激酶;GSK-3β:糖原合成酶激酶3β;APC:adenomatous polyposis coli,结肠腺瘤性息肉病蛋白;α-SMA:α-平滑肌肌动蛋白;E-cadherin:E-钙黏蛋白
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