Role of moesin in renal fibrosis.

Abstract

BACKGROUND:

Renal 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.

METHOD:

Human 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.

RESULT:

HK-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.

CONCLUSION:

We find that moesin might be involved in renal fibrosis and its effects could be related to interacting with E-Cadherin.

• Authors: Yong-Xi Chen, Wen Zhang, Wei-Ming Wang, Xia-Lian Yu, Yi-Mei Wang, Min-Jun Zhang, Nan Chen
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e112936 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25406076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ACTA2 protein, human
• Actins
• Cadherins
• Microfilament Proteins
• RNA, Small Interfering
• Transforming Growth Factor beta1
• moesin

Topics

• Actins (metabolism)
• Analysis of Variance
• Animals
• Blotting, Western
• Cadherins (metabolism)
• Cell Line
• Fibrosis (metabolism)
• Humans
• Immunohistochemistry
• Microfilament Proteins (metabolism)
• Phosphorylation
• RNA, Small Interfering (genetics)
• Rats
• Real-Time Polymerase Chain Reaction
• Renal Insufficiency, Chronic (metabolism, pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• Transforming Growth Factor beta1