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Seven Steps to Stellate Cells
Published on: May 10, 2011
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O-GlcNAcylation inhibits hepatic stellate cell activation
Rui Li1,2, Qunxiang Ong2, Chi Chun Wong1
1Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
Journal of Gastroenterology and Hepatology
|September 21, 2021
Summary
O-GlcNAc transferase (OGT) inhibits liver fibrosis by suppressing hepatic stellate cell activation. OGT promotes O-GlcNAcylation of SRF, reducing its activity and protecting the liver.
Area of Science:
- Biochemistry
- Cell Biology
- Hepatology
Background:
- Protein O-GlcNAcylation is a crucial post-translational modification impacting gene expression and cell functions.
- O-GlcNAc transferase (OGT) plays a significant role in liver pathophysiology and disease development.
Purpose of the Study:
- To investigate the role of OGT in hepatic stellate cells (HSCs).
- To determine the impact of OGT on liver fibrosis progression.
Main Methods:
- Primary HSCs isolated from mice.
- Liver fibrosis induced by CCl4 or MCD diet.
- RNA sequencing, luciferase reporter assays, and immunofluorescence staining were employed.
Main Results:
- OGT expression and O-GlcNAcylation were reduced in fibrotic livers and HSCs.
- OGT knockdown modulated HSC activation pathways.
- OGT repressed SRF activity, inhibiting α-SMA transcription, with mutations reversing this effect.
Conclusions:
- OGT acts as a negative regulator of HSC activation.
- OGT protects against liver fibrosis by promoting SRF O-GlcNAcylation.
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