Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines.
Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines.
复制标题
肝纤维化：从机制到药物靶向过氧化物酶体增殖物激活受体α
DOI：
10.1097/hep.0000000000000182
复制
发表时间：
2023-11-01
期刊：
影响因子：
13.5
通讯作者：
Li, Guolin
中科院分区：
文献类型：
--
作者：
Gong, Lijun;Wei, Fang;Gonzalez, Frank J.;Li, Guolin
肝纤维化是持续的慢性肝损伤和炎症导致肝细胞死亡，继而形成纤维瘢痕的结果，这是NASH和酒精性脂肪性肝炎的特征，可导致肝硬化、肝癌和肝功能衰竭。虽然在了解肝纤维化的发病机制和临床后果方面取得了进展，但对这种疾病的治疗策略有限。临床前研究表明，过氧化物酶体增殖物激活受体α通过激活与解毒脂毒性和毒素相关的基因，转录抑制炎症相关基因，以及抑制肝星状细胞的激活，在预防肝纤维化的发展中发挥重要作用。鉴于强大的临床前数据，几种过氧化物酶体增殖物激活受体α激动剂已经在肝纤维化的临床试验中进行了测试。在这里，我们提供了最新的进展，了解了过氧化体增殖物激活受体α预防纤维化的机制，并讨论了靶向PPARα用于抗纤维化治疗的可能性。
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.
影响因子：
13.5
作者：
Fletcher, Nicola F.;Sutaria, Rupesh;Jo, Juandy;Barnes, Amy;Blahova, Miroslava;Meredith, Luke W.;Cosset, Francois-Loic;Curbishley, Stuart M.;Adams, David H.;Bertoletti, Antonio;McKeating, Jane A.
通讯作者：
McKeating, Jane A.
DOI：
10.4093/kdj.2010.34.5.274
发表时间：
2010-10
期刊：
Korean diabetes journal
影响因子：
--
作者：
Jeoung NH;Harris RA
通讯作者：
Harris RA