HUWE1 promotes EGFR ubiquitination and degradation to protect against renal tubulointerstitial fibrosis
HUWE1 promotes EGFR ubiquitination and degradation to protect against renal tubulointerstitial fibrosis
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HUWE1促进EGFR泛素化和降解以预防肾小管间质纤维化
DOI：
10.1096/fj.201902751r
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Liang Xiubin
中科院分区：
文献类型：
--
作者：
Zhu Qian;Dong Hao;Bukhari Ashfaq-Ahmad-Shah;Zhao Anran;Li Min;Sun Yifei;Zhang Xue;Cao Changchun;Su Dongming;Liang Xiubin
肾小管上皮细胞损伤是与小管间质纤维化和其他肾脏疾病相关的致病性的一个关键特征。HUWE1是一种E3泛素连接酶，通过参与泛素化和靶蛋白的降解来起作用。然而，HUWE1调节肾小管上皮细胞纤维化的详细机制尚未确定。本研究通过检测HUWE1和EGFR在单侧输尿管梗阻（UUO）小鼠中的表达，探讨HUWE1对肾小管间质纤维化的可能调控作用。在UUO损伤后，肾脏中HUWE1和EGFR蛋白和mRNA水平的表达明显一致。表达HUWE1可抑制TGF - β -诱导的HK - 2细胞损伤，而过表达HUWE1可降低EGFR的表达。进一步分析表明，HUWE1与EGFR发生物理相互作用，促进其泛素化和降解。HUWE1的表达在肾脏疾病中也有临床意义，在多种临床肾病中HUWE1的表达明显降低，而EGFR的表达与正常肾脏相比明显升高。因此，本研究表明，HUWE1作为EGFR特异性的E3泛素连接酶，促进EGFR泛素化和降解，从而调节EGFR表达，对肾损伤具有保护作用。
Injury of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. HUWE1, an E3 ubiquitin ligase, acts by participating in ubiquitination and degradation of its target proteins. However, the detailed mechanisms by which HUWE1 might regulate fibrosis in renal tubular epithelial cells have not been established. Here, the possible regulation of renal tubulointerstitial fibrosis by HUWE1 was investigated by examining the expression of HUWE1 and EGFR in unilateral ureteral obstruction (UUO) mice. Markedly consistent reciprocal changes in HUWE1 and EGFR expression were observed at the protein and mRNA levels in the kidney after UUO injury. Expression of HUWE1 inhibited TGF‐β‐induced injury to HK‐2 cells, while HUWE1 overexpression decreased the expression of EGFR. Further analysis indicated that HUWE1 physically interacted with EGFR and promoted its ubiquitination and degradation. HUWE1 expression also showed clinical relevance in renal disease, as it notably decreased in multiple types of clinical nephropathy, while EGFR expression significantly increased when compared to the normal kidney. Therefore, this study demonstrated that HUWE1, which serves as an E3 ubiquitin ligase specific for EGFR, promotes EGFR ubiquitination and degradation, thereby regulating EGFR expression and providing protection against kidney injury.
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影响因子：
8.8
作者：
Rego, R. L.;Foster, N. R.;Smyrk, T. C.;Le, M.;O'Connell, M. J.;Sargent, D. J.;Windschitl, H.;Sinicrope, F. A.
通讯作者：
Sinicrope, F. A.
DOI：
10.1042/bcj20160582
发表时间：
2017-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Preston GM;Brodsky JL
通讯作者：
Brodsky JL
影响因子：
8.3
作者：
Border, WA;Noble, NA
通讯作者：
Noble, NA
影响因子：
78.5
作者：
N. Hynes;H. Lane
通讯作者：
N. Hynes;H. Lane
影响因子：
4
作者：
Hui You;Yamei Ge;Jian Zhang;Yizhi Cao;Jing Xing;D. Su;Yujie Huang;Min Li;Shen Qu;F. Sun;Xiubin Liang
通讯作者：
Hui You;Yamei Ge;Jian Zhang;Yizhi Cao;Jing Xing;D. Su;Yujie Huang;Min Li;Shen Qu;F. Sun;Xiubin Liang