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HERO ID
7508092
Reference Type
Journal Article
Title
Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB
Author(s)
Huang, Z; Mou, T; Luo, Y; Pu, X; Pu, J; Wan, L; Gong, J; Yang, H; Liu, Y; Li, Z; Shen, A; Wu, Z
Year
2020
Is Peer Reviewed?
Yes
Journal
Cell Death & Disease
ISSN:
2041-4889
Volume
11
Issue
6
Page Numbers
455
Language
English
PMID
32532961
DOI
10.1038/s41419-020-2648-0
Abstract
Hepatic ischemia/reperfusion injury (IRI) is an unavoidable course in liver transplantation, during which the immune response of inflammation plays a leading part. MicroRNA-450b-5p (miR-450b-5p), which has been reported to participate in several inflammatory diseases, was investigated in this study. The purpose of this study is to identify the potential function of miR-450b-5p toward remission of hepatic IRI and elucidate the specific mechanism. Herein we found that expression of miR-450b-5p, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 was stimulated in hepatic IRI. Inhibition of miR-450b-5p could remarkably alleviate mouse hepatic IRI and improve liver function measured by hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA). We further assessed protein expression undergoing Western blot and immunofluorescence, and discovered that miR-450b-5p suppressed alpha B-crystallin (CRYAB), thus restraining the inhibitory κB kinase (IKK) β-mediated canonical nuclear factor-κB (NF-κB) signaling, instead of the noncanonical path guided by IKKα in hepatic IRI. In addition, we demonstrated CRYAB as an activator of M2 polarization through protein kinase B (Akt) 1/mammalian target of rapamycin (mTOR), thus resulting in relief of liver IRI. Combination treatment containing both paths revealed a better antidamage efficacy than adjusting either path alone, suggesting that the joint therapy might be a promising solution in hepatic IRI.
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