Journal article
Moesin, an Ezrin/Radixin/Moesin Family Member, Regulates Hepatic Fibrosis
Hepatology (Baltimore, Md.), Vol.72(3), pp.1073-1084
09/2020
DOI: 10.1002/hep.31078
PMCID: PMC7437180
PMID: 31860744
Abstract
Background and Aims
Moesin, an ezrin/radixin/moesin family member, is involved in the regulation of cell adhesion, polarity, and migration by cross‐linking between the actin cytoskeleton and plasma membrane. The primary effector cell in hepatic fibrosis is the hepatic stellate cell (HSC), which undergoes activation during liver injury leading to increased extracellular matrix production.
Approach and Results
Here, we have hypothesized that moesin plays a critical role in linking the HSC cytoskeleton to the fibrogenic cascade during HSC activation. Moesin phosphorylation was up‐regulated during HSC activation and fibrogenesis. Using moesin wild‐type (WT) and mutant constructs (phosphomimicking T558D and nonphosphorylatable T558A), we found that cellular motility and contraction were increased in moesin WT‐infected and T558D‐infected cells, paralleled by an increase in smooth muscle α‐actin and collagen 1 expression. In contrast, overexpression of nonphosphorylatable moesin and moesin knockout (KO) decreased cellular motility and contraction. Most importantly, moesin KO led to abrogation of liver fibrosis. The mechanism of moesin's effect was a reduction in myocardin‐related transcription factor‐A and serum‐response factor (SRF)–mediated changes in the actin cytoskeleton, which in turn modulated the expression of matrix genes.
Conclusions
Taken together, our findings suggest that the linkage between cytoskeletal dynamics and the correlated MRTF/SRF signaling pathway has a pivotal role in HSC activation and fibrogenesis.
Details
- Title: Subtitle
- Moesin, an Ezrin/Radixin/Moesin Family Member, Regulates Hepatic Fibrosis
- Creators
- Serhan Karvar - Medical University of South CarolinaEphraim A. Ansa-Addo - MUSC Hollings Cancer CenterJo Suda - Cedars-Sinai Medical CenterShweta Singh - Medical University of South CarolinaLixin Zhu - University at Buffalo, State University of New YorkZihai Li - MUSC Hollings Cancer CenterDon C. Rockey - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.72(3), pp.1073-1084
- DOI
- 10.1002/hep.31078
- PMID
- 31860744
- PMCID
- PMC7437180
- NLM abbreviation
- Hepatology
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Number of pages
- 12
- Language
- English
- Date published
- 09/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695827702771
Metrics
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