Pluto Bioinformatics

GSE157156: Liver Epithelial Focal Adhesion Kinase Modulates Fibrogenesis and Hedgehog Signaling

Bulk RNA sequencing

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix-integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in non-malignant non-motile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic liver. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lack FAK in liver epithelial cells develop more severe liver injury and worse fibrosis as compared to controls. Increased fibrosis in liver epithelial FAK-deficient mice is linked to the activation of several pro-fibrotic pathways, including the hedgehog-smoothened pathway. FAK-deficient hepatocytes produce increased Indian hedgehog in a matrix stiffness-dependent manner. Furthermore, there is increased expression of the hedgehog receptor, smoothened, in macrophages and biliary cells of hepatocyte-specific FAK-deficient fibrotic liver. These results indicate that liver epithelial FAK has important regulatory roles in the response to liver injury and progression of fibrosis. SOURCE: Tammy,T,Chang (Tammy.chang@ucsf.edu) - liver tissue engineering UCSF

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