Role of moesin in renal fibrosis.

Yong-Xi Chen,Xia-Lian Yu,Nan Chen,Yi-Mei Wang,Min-Jun Zhang,Wen Zhang,Wei-Ming Wang,Aristidis S. Charonis

doi:10.1371/journal.pone.0112936

Abstract

BackgroundRenal fibrosis is the final common pathway of chronic kidney disease (CKD). Moesin is a member of Ezrin/Radixin/Moesin (ERM) protein family but its role in renal fibrosis is not clear.MethodHuman proximal tubular cells (HK-2) were stimulated with or without TGF-β1. Moesin and downstream target genes were examined by real-time PCR and western blot. Phosphorylation of moesin and related signaling pathway was investigated as well. Rat model of unilateral ureteral obstruction (UUO) was established and renal moesin was examined by immunohistochemistry. Moesin in HK-2 cells were knocked down by siRNA and change of downstream genes in transfected HK-2 cells was studied. All animal experiments were reviewed and approved by the Ethics Committee for animal care of Ruijin Hospital.ResultHK-2 cells stimulated with TGF-β1 showed up-regulated level of α-SMA and down-regulated level of E-Cadherin as well as elevated mRNA and protein level of moesin. In rat model of UUO, renal moesin expression increased in accordance with severity of tubulointerestital fibrosis in the kidneys with ureteral ligation while the contralateral kidneys were normal. Further study showed that TGF-β1 could induce phosphorylation of moesin which depended on Erk signaling pathway and Erk inhibitor PD98059 could block moesin phosphorylation. Effects of TGF-β1 on moesin phosphorylation was prior to its activation to total moesin. RNA silencing studies showed that knocking down of moesin could attenuate decrease of E-Cadherin induced by TGF-β1.ConclusionWe find that moesin might be involved in renal fibrosis and its effects could be related to interacting with E-Cadherin.

Highlights

Chronic kidney disease (CKD) has received increased attention for its socioeconomic burden and for its impact on the global public health
We find that moesin might be involved in renal fibrosis and its effects could be related to interacting with ECadherin
Irrespective of the underlying causes, progressive chronic kidney disease (CKD) often leads to renal fibrosis which is characterized as glomerulosclerosis and tubulointerstitial fibrosis histologically, and end-stage renal disease (ESRD) that requires costly renal replacement therapy clinically [1,2]

Summary

Introduction

Chronic kidney disease (CKD) has received increased attention for its socioeconomic burden and for its impact on the global public health. Irrespective of the underlying causes, progressive CKD often leads to renal fibrosis which is characterized as glomerulosclerosis and tubulointerstitial fibrosis histologically, and end-stage renal disease (ESRD) that requires costly renal replacement therapy clinically [1,2]. Given this background, further investigating molecular details of renal fibrosis would help to provide comprehensive understanding of the disease and therapeutic strategies. Moesin is a member of Ezrin/Radixin/Moesin (ERM) protein family that acts as cross linker between plasma membrane and the actin cytoskeleton [3,4]. Moesin is a member of Ezrin/ Radixin/Moesin (ERM) protein family but its role in renal fibrosis is not clear

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Results

Conclusion