Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice
Open accessAbstract
Liver injury stimulates hepatocyte replication and hepatic stellate cell (HSC) activation, thereby driving liver regeneration. Aberrant HSC activation induces liver fibrosis. However, mechanisms underlying liver regeneration and fibrosis remain poorly understood. Here, we identify hepatic Snai1 and Snai2 as important transcriptional regulators for liver regeneration and fibrosis. Partial hepatectomy or CCl4 treatment increases occupancies of Snai1 and Snai2 on cyclin A2 and D1 promoters in the liver. Snai1 and Snai2 in turn increase promoter H3K27 acetylation and cyclin A2/D1 expressions. Hepatocyte-specific deletion of both Snai1 and Snai2, but not one alone, suppresses liver cyclin A2/D1 expression and regenerative hepatocyte proliferation after hepatectomy or CCl4 treatments but augments CCl4-stimulated HSC activation and liver fibrosis. Conversely, Snai2 overexpression in the liver enhances hepatocyte replication and suppresses liver fibrosis after CCl4 treatment. These results suggest that hepatic Snai1 and Snai2 directly promote, via histone modifications, reparative hepatocyte replication and indirectly inhibit liver fibrosis.
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The differential regulation of Snai1 and Snai2 is highly associated with the proliferation response of hepatocytes.
“Interestingly, the differential regulation of Snai1 and Snai2 is highly associated with the proliferation response of hepatocytes [62].”
From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [62]
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- Authors
- Wang, P., Kang, Q., Wu, W.-S., & Rui, L.
- Affiliations
- Guangdong University of Technology (CN)
- University of Michigan (US)
- Corresponding author
- Rui, Liangyou
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 43
- Issue
- 3
- Pages
- 113875
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC11025633
- OpenAlex
- W4392637080
- Cited by
- 20
- References
- 33
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 2
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Michigan (RO1 DK130111, RO1 DK127568, RO1 DK114220)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034933)
- University of Michigan Center for Gastrointestinal Research
- National Institutes of Health (DK020572)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- SNAI1, SNAI2, liver regeneration, liver fibrosis, hepatic stellate cell activation, hepatocyte proliferation, cyclin A2, cyclin D1, H3K27 acetylation, histone modifications, transcriptional regulation, partial hepatectomy, carbon tetrachloride-induced liver injury, hepatocyte-specific deletion
- MeSH terms
- Snail Family Transcription Factors, Animals, Hepatectomy, Liver, Liver Cirrhosis, Liver Regeneration, Mice, Cyclin A2
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