Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines

Liver fibrosis is the result of sustained chronic liver injury and inflammation leading to hepatocyte cell death followed by the formation of fibrous scars, which is the hallmark of NASH and alcoholic steatohepatitis and can lead to cirrhosis, HCC, and liver failure. Although progress has been made...

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Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 2023-11, Vol.78 (5), p.1625-1653
Hauptverfasser: Gong, Lijun, Wei, Fang, Gonzalez, Frank J, Li, Guolin
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container_title Hepatology (Baltimore, Md.)
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creator Gong, Lijun
Wei, Fang
Gonzalez, Frank J
Li, Guolin
description Liver fibrosis is the result of sustained chronic liver injury and inflammation leading to hepatocyte cell death followed by the formation of fibrous scars, which is the hallmark of NASH and alcoholic steatohepatitis and can lead to cirrhosis, HCC, and liver failure. Although progress has been made in understanding the pathogenesis and clinical consequences of hepatic fibrosis, therapeutic strategies for this disease are limited. Preclinical studies suggest that peroxisome proliferator-activated receptor alpha plays an important role in preventing the development of liver fibrosis by activating genes involved in detoxifying lipotoxicity and toxins, transrepressing genes involved in inflammation, and inhibiting activation of hepatic stellate cells. Given the robust preclinical data, several peroxisome proliferator-activated receptor alpha agonists have been tested in clinical trials for liver fibrosis. Here, we provide an update on recent progress in understanding the mechanisms by which peroxisome proliferator-activated receptor alpha prevents fibrosis and discuss the potential of targeting PPARα for the development of antifibrotic treatments.
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subjects Carcinoma, Hepatocellular - pathology
Fibrosis - etiology
Fibrosis - genetics
Fibrosis - metabolism
Humans
Inflammation - metabolism
Liver - pathology
Liver Cirrhosis - drug therapy
Liver Cirrhosis - etiology
Liver Cirrhosis - metabolism
Liver Neoplasms - pathology
Non-alcoholic Fatty Liver Disease - pathology
PPAR alpha - genetics
PPAR alpha - metabolism
title Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines
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