RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis - PubMed
7 hours ago
- #Liver Fibrosis
- #Hepatic Stellate Cells
- #LARP6
- LARP6, an RNA-binding protein, is upregulated in activated hepatic stellate cells (HSCs) in metabolic dysfunction-associated steatohepatitis (MASH) and MetALD.
- JUNB was found to upregulate LARP6 expression in activated HSCs, as shown by snRNA/ATAC-sequencing.
- Knockdown of LARP6 in human HSCs suppressed fibrogenic gene expression.
- LARP6 interacts with mature mRNAs of over 300 genes, including COL1A1, COL1A2, and COL3A1, to regulate mRNA expression and translation.
- LARP6 protein-protein interactions include mRNA translation components and the actin cytoskeleton, as demonstrated by IP-MS analysis.
- HSC-specific knockdown or pharmacological inhibition of LARP6 attenuated fibrosis development in human MASH and MetALD liver spheroids.
- Targeting LARP6 in human HSCs may represent a therapeutic approach for liver fibrosis.