1. Academic Validation
  2. Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

  • Cell Death Dis. 2020 Jun 12;11(6):455. doi: 10.1038/s41419-020-2648-0.
Zuotian Huang 1 Tong Mou 1 Yunhai Luo 1 Xingyu Pu 2 Junliang Pu 1 Lei Wan 3 Junhua Gong 1 Hang Yang 1 Yanyao Liu 1 Zhongtang Li 1 Ai Shen 4 Zhongjun Wu 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 West China School of Medicine, Sichuan University, Chongqing, China.
  • 3 Phase I Clinical Trial Ward, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 5 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. wzjtcy@126.com.
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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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10172
    99.51%, IKKβ 抑制剂
    IKK