Hepatocellular Brg1 promotes CCl4-induced liver inflammation, ECM accumulation and fibrosis in mice

Baocai Wang, Benedikt Kaufmann, Carolin Mogler, Suyang Zhong, Yuhan Yin, Zhangjun Cheng, Roland M. Schmid, Helmut Friess, Norbert Hüser, Guido von Figura, Daniel Hartmann

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction Hepatic fibrosis is a progressive pathological process involving the exhaustion of hepatocellular regenerative capacity and ultimately leading to the development of cirrhosis and even hepatocellular carcinoma. Brg1, the core subunit of the SWI/SNF chromatin-remodeling complex, was recently identified as important for liver regeneration. This study investigates the role of Brg1 in hepatic fibrosis development. Methods Hepatocyte-specific Brg1 knockout mice were generated and injected with carbon tetrachloride (CCl4) for 4, 6, 8, and 12 weeks to induce liver fibrosis. Afterwards, liver fibrosis and liver damage were assessed. Results Brg1 expression was significantly increased in the fibrotic liver tissue of wild-type mice, as compared to that of untreated wild-type mice. The livers of the Brg1 knockout animals showed reduced liver inflammation, extracellular matrix accumulation, and liver fibrosis. TNF-α and NF-κB-mediated inflammatory response was reduced in Brg1 knockout animals. Conclusion Brg1 promotes the progression of liver fibrosis in mice and may therefore be used as a potential therapeutic target for treating patients with liver fibrosis due to chronic injury.

Original languageEnglish
Article numbere0294257
JournalPLoS ONE
Volume18
Issue number11 November
DOIs
StatePublished - Nov 2023
Externally publishedYes

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