MicroRNA-21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Jorge Matias CavigliaRobert F Schwabe

Abstract

Fibrosis and cancer represent two major complications of chronic liver disease. MicroRNAs have been implicated in the development of fibrosis and cancer, thus constituting potential therapeutic targets. Here, we investigated the role of microRNA-21 (miR-21), a microRNA that has been implicated in the development of fibrosis in multiple organs and has also been suggested to act as an "oncomir." Accordingly, miR-21 was the microRNA that showed the strongest up-regulation in activated hepatic stellate cells (HSCs) in multiple models of fibrogenesis, with an 8-fold to 24-fold induction compared to quiescent HSCs. However, miR-21 antisense inhibition did not suppress the activation of murine or human HSCs in culture or in liver slices. Moreover, genetic deletion of miR-21 in two independently generated knockout mice or miR-21 antisense inhibition did not alter HSC activation or liver fibrosis in models of toxic and biliary liver injury. Despite a strong up-regulation of miR-21 in injury-associated hepatocellular carcinoma and in cholangiocarcinoma, miR-21 deletion or antisense inhibition did not reduce the development of liver tumors. As inhibition of the most up-regulated microRNA did not affect HSC activation, liver fibrosis, or f...Continue Reading

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Citations

Jan 10, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sanchuan Lai, Yasuko Iwakiri
Apr 2, 2019·Rheumatology·Xiao-Bo WangXin Zheng
Jan 25, 2020·Artificial Cells, Nanomedicine, and Biotechnology·Wang CuiqiongJiang Yinyan
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Feb 23, 2020·Frontiers in Medicine·Ting ZhangSuthat Liangpunsakul
Aug 29, 2020·European Journal of Pharmacology·Devaraj Ezhilarasan
Jan 3, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Dejuan XiangHao Zhang
Nov 17, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Qiang ZhangShuZhe Ding
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Feb 4, 2022·Nutrition Research Reviews·Zixuan ZhangJ Bernadette Moore

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