Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 885, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173507
Keywords
MicroRNA; Hepatic stellate cells; Hepatic fibrosis; Extracellular matrix; Collagen
Categories
Funding
- Indian Council of Medical Research, New Delhi, India [2020-4160]
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Hepatic stellate cells (HSCs) activation play a significant role in the progression of hepatic fibrosis. During chronic liver diseases, hepatocytes are damaged severely and secrete several pro-inflammatory markers and profibrogenic cytokines via modulation of a variety of signaling pathways that are responsible for the activation of HSCs. The microRNAs (miRNA or miR) have the potential to modulate fibrogenic signaling pathways in HSCs. A variety of miRNAs are identified as profibrogenic and are capable of activating HSCs by modulating fibrosis associated signaling pathways such as transforming growth factor-beta/Smad, Wnt/beta-catenin, Hedgehog, Snail and Notch in the injured liver. On the other hand, HSCs also have certain antifibrotic miRNAs and these include miR16, miR-19b, miR-29, miR-30, miR-101, miR-122, miR-133a, miR-144, miR-146a, miR-150-5p, miR-155, miR195, miR-200a, miR-214, miR-335, miR-370, miR-454, miR-483, etc. are responsible for maintenance of the quiescent phenotype of normal HSCs, apoptosis induction and phenotypic reversion of activated HSCs, inhibition of HSCs proliferation, suppression of the extracellular matrix-associated gene expressions, etc. Thus, understanding of HSCs specific miRNAs regulation may provide new ideas for the targeted therapy of hepatic fibrosis at molecular level in the near future. Therefore, this review focusses on the modulation of miRNAs profile during the HSCs activation in the fibrotic liver.
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