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Seven Steps to Stellate Cells
Published on: May 10, 2011
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A cAbl-MRTF-A Feedback Loop Contributes to Hepatic Stellate Cell Activation.
Yunjie Lu1, Fangqiao Lv2, Ming Kong3
1Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Frontiers in Cell and Developmental Biology
|November 5, 2019
Summary
A positive feedback loop between c-Abl and myocardin-related transcription factor A (MRTF-A) drives hepatic stellate cell activation, a key process in liver fibrosis development.
Area of Science:
- Hepatology
- Cell Biology
- Molecular Biology
Background:
- Hepatic stellate cell (HSC) trans-differentiation into myofibroblasts is central to liver fibrosis.
- Myocardin-related transcription factor A (MRTF-A) is a known regulator of HSC activation.
Purpose of the Study:
- To investigate the interplay between MRTF-A and the tyrosine kinase c-Abl in HSC activation and liver fibrosis.
Main Methods:
- Utilized MRTF-A knockout (KO) mice and wild-type (WT) littermates in various liver fibrosis models.
- Performed *in vitro* studies involving HSC knockdown and pharmaceutical inhibition.
- Analyzed gene promoter binding and protein interactions, including ERK pathway activation.
Main Results:
- c-Abl expression was downregulated in MRTF-A KO mice and upon MRTF-A knockdown in HSCs.
- MRTF-A directly activated the *Abl1* promoter via Sp1 interaction.
- c-Abl inhibition suppressed MRTF-A activity; c-Abl activated ERK, which phosphorylated and promoted MRTF-A nuclear translocation.
Conclusions:
- A positive feedback loop exists between c-Abl and MRTF-A, promoting HSC activation.
- This c-Abl-MRTF-A loop is a significant contributor to the pathogenesis of liver fibrosis.
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