GSE279064

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Summary

Metabolic syndrome and excessive alcohol consumption result in liver injury and fibrosis, which is characterized by an increased collagen production by activated Hepatic Stellate Cells (HSCs). LARP6, an RNA-binding protein, was shown to facilitate collagen production. However, LARP6 expression and functionality as a regulator of fibrosis development in a disease relevant model remains elusive. By using snRNA-seq, we show that LARP6 and collagen-associated genes are upregulated mainly in HSCs of hepatic fibrosis patients. Moreover, LARP6 knockdown in isolated HSCs suppressed fibrogenic genes expression. By integrating eCLIP analysis and ribosome profiling in HSCs, we show that LARP6 interacts with mature mRNAs comprising over three hundred genes, including RNA structural elements within COL1A1, COL1A2, and COL3A1 to regulate mRNA expression and translation. Furthermore, LARP6 reduction attenuates fibrosis in human liver spheroids. Altogether, our results suggest that targeting LARP6 in human HSCs may provide new strategies for anti-fibrotic prevention and therapy.