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

PLoS One. 2023 Nov 30;18(11):e0294257. doi: 10.1371/journal.pone.0294257. eCollection 2023.

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.

MeSH terms

  • Animals
  • Carbon Tetrachloride / toxicity
  • Carcinoma, Hepatocellular* / pathology
  • Extracellular Matrix / metabolism
  • Fibrosis
  • Hepatitis* / pathology
  • Inflammation / pathology
  • Liver / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Neoplasms* / pathology
  • Mice
  • Mice, Knockout

Substances

  • Carbon Tetrachloride
  • Smarca4 protein, mouse

Grants and funding

Wilhelm Sander Stiftung: Grant to DH, GvF The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.