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• W3012929925 abstract "The lipid-storage hepatic stellate cell (HSC) plays a pivotal role in liver fibrosis being able to trans-differentiate into myofibroblasts in response to various pro-fibrogenic stimuli. In the present study we investigated the role of CDKN2a/p16, a negative regulator of cell cycling, in HSC activation and the underlying mechanism. Levels of p16 were significantly down-regulated in activated HSCs isolated from mice induced to develop liver fibrosis compared to quiescent HSCs isolated from the control mice ex vivo. There was a similar decrease in p16 expression in cultured HSCs undergoing spontaneous activation or exposed to TGF- treatment in vitro. More important, p16 down-regulation was observed to correlate with cirrhosis in humans. In a classic model of carbon tetrachloride (CCl4) induced liver fibrosis, fibrogenesis was far more extensive in mice with p16 deficiency (KO) than the wild type (WT) littermates. Depletion of p16 in cultured HSCs promoted the synthesis of extracellular matrix (ECM) proteins. Mechanistically, p16 deficiency accelerated reactive oxygen species (ROS) generation in HSCs likely through the p38 MAPK signaling. P38 inhibition or ROS cleansing attenuated ECM production in p16 deficient HSCs. Taken together, our data unveil a previously unappreciated role for p16 in the regulation of HSC activation. Screening for small-molecule compounds that can boost p16 activity may yield novel therapeutic strategies against liver fibrosis." @default.
• W3012929925 created "2020-03-27" @default.
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• W3012929925 date "2020-03-24" @default.
• W3012929925 modified "2023-10-18" @default.
• W3012929925 title "CDKN2a/p16 Antagonizes Hepatic Stellate Cell Activation and Liver Fibrosis by Modulating ROS Levels" @default.
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• W3012929925 doi "https://doi.org/10.3389/fcell.2020.00176" @default.
• W3012929925 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7105638" @default.
• W3012929925 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32266258" @default.
• W3012929925 hasPublicationYear "2020" @default.
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