The role of hepatic stellate cell (HSC) activation and liver fibrosis in metabolic-dysfunction-associated steatohepatitis (MASH) has been further elucidated. A study found that knockdown of TM7SF3 accelerates HSC activation in liver organoids and in MASH mice, leading to increased HSC proliferation and liver fibrosis. This effect is attributed to TM7SF3’s role in inhibiting the splicing factor heterogeneous nuclear ribonucleoprotein U (hnRNPU), which facilitates the generation of a more active form of TEAD1 by excluding its inhibitory exon 5.
Inhibition of TEAD1 splicing using a specific antisense oligomer (ASO) was shown to reduce HSC activation and liver fibrosis in MASH models. These findings highlight TM7SF3’s critical role in modulating HSC activation and fibrosis progression by influencing TEAD1 splicing. Targeting TEAD1 splicing could be a promising strategy for managing liver fibrosis associated with MASH.
Reference: Isaac R, Bandyopadhyay G, Rohm TV, et al. TM7SF3 controls TEAD1 splicing to prevent MASH-induced liver fibrosis. Cell Metab. 2024 May 7;36(5):1030-1043.e7. doi: 10.1016/j.cmet.2024.04.003. Epub 2024 Apr 25. PMID: 38670107; PMCID: PMC11113091.
