Related Experiment Video
Updated: Jun 9, 2026
08:19
Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
Published on: April 22, 2019
MRC2 Links Collagen Turnover to Integrin/PI3K/AKT-Driven Fibrogenesis
Nuchanart Suntornnont1,2,3, Jiranuwat Sapudom4, Chaiyaboot Ariyachet1,2,3
1Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Advanced Biology
|June 8, 2026
Summary
Mannose receptor C-type 2 (MRC2) negatively regulates liver fibrosis by suppressing hepatic stellate cell activation. MRC2 deficiency promotes collagen production and pro-fibrotic signaling pathways, highlighting its therapeutic potential.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Biology
Background:
- Liver fibrosis involves excessive collagen deposition by activated hepatic stellate cells (HSCs).
- The collagen-binding role of mannose receptor C-type 2 (MRC2) is known, but its function in HSC activation signaling is unclear.
Purpose of the Study:
- To investigate the non-canonical signaling role of MRC2 in regulating HSC activation.
- To determine MRC2's impact on pro-fibrotic pathways and collagen production.
Main Methods:
- Utilized doxycycline-inducible knockdown and overexpression systems in human HSCs.
- Performed transcriptomic analysis to identify affected signaling pathways.
- Employed pharmacological inhibitors for PI3K and integrins to validate mechanistic findings.
Main Results:
- MRC2 deficiency enhanced HSC activation, including proliferation, migration, and collagen overproduction.
- MRC2 overexpression suppressed these pro-fibrotic phenotypes.
- Transcriptomic analysis revealed MRC2 depletion activated ECM organization, collagen biosynthesis, and PI3K/AKT signaling.
- Inhibition of PI3K or integrins reversed MRC2 depletion-induced phenotypes.
Conclusions:
- MRC2 acts as a novel, non-canonical negative regulator of HSC activation.
- MRC2 signaling influences HSC activation through the integrin/PI3K/AKT pathway.
- Targeting MRC2 may offer a therapeutic strategy for liver fibrosis.
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