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  • Title: Targeting ribosomal S-6 kinase for the prevention and treatment of liver injury and liver fibrosis.
    Author: Buck M.
    Journal: Drug News Perspect; 2008; 21(6):301-6. PubMed ID: 18836586.
    Abstract:
    Activation of hepatic stellate cells (HSC) is responsible for the development of liver fibrosis in chronic liver diseases of all causes, and remarkably, HSC clearance by apoptosis may allow recovery from liver injury and reversal of liver fibrosis. Because in preclinical studies it has been shown that activation of ribosomal S-6 kinase (RSK) and phosphorylation of the CCAAT/enhancer-binding protein (C/EBP) beta in activated HSC is critical for the progression of liver fibrosis, RSK has been considered as a therapeutic target for the liver fibrosis. Unexpectedly, preclinical studies documented a strong antiinflammatory effect of RSK inhibitors, decreasing liver injury induced by hepatotoxins. Therefore, RSK inhibitors reduce liver fibrosis directly by inducing apoptosis of activated HSC, and indirectly by preventing liver injury and inflammation. The activation of RSK and C/EBPbeta phosphorylation also occurs in human liver fibrosis. Thus, appropriate RSK inhibitors may be beneficial in the prevention and treatment of liver injury and liver fibrosis. These issues will be discussed in this review.
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