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ACS Chem Biol ; 17(4): 918-929, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35274923

ABSTRACT

Liver fibrosis progression in chronic liver disease leads to cirrhosis, liver failure, or hepatocellular carcinoma and often ends in liver transplantation. Even with an increased understanding of liver fibrogenesis and many attempts to generate therapeutics specifically targeting fibrosis, there is no approved treatment for liver fibrosis. To further understand and characterize the driving mechanisms of liver fibrosis, we developed a high-throughput genome-wide CRISPR/Cas9 screening platform to identify hepatic stellate cell (HSC)-derived mediators of transforming growth factor (TGF)-ß-induced liver fibrosis. The functional genomics phenotypic screening platform described here revealed the novel biology of TGF-ß-induced fibrogenesis and potential drug targets for liver fibrosis.


Subject(s)
Hepatic Stellate Cells , Transforming Growth Factor beta , Fibrosis , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Humans , Liver/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Signal Transduction , Transforming Growth Factor beta/adverse effects , Transforming Growth Factor beta/metabolism
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