FAM49B, restrained by miR-22, relieved hepatic ischemia/reperfusion injury by inhibiting TRAF6/IKK signaling pathway in a Rac1-dependent manner

  • Mol Immunol. 2022 Mar;143:135-146. doi: 10.1016/j.molimm.2022.01.015.
Zuotian Huang  1 ,  Junliang Pu  2 ,  Yunhai Luo  2 ,  Jing Fan  2 ,  Kaili Li  2 ,  Dadi Peng  2 ,  Kezhen Zong  2 ,  Baoyong Zhou  2 ,  Xiangdong Guan  3 ,  Fachun Zhou  4
Affiliations
  • 1. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 2. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3. Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 4. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 35131594 DOI: 10.1016/j.molimm.2022.01.015
Abstract

Hepatic ischemia/reperfusion (I/R) injury plays a pivotal pathogenic role in trauma, hepatectomy, and liver transplantation. However, the whole mechanism remains undescribed. The objective of this study is to investigate the internal mechanism by which microRNA-22 (miR-22) targets family with sequence similarity 49 member B (FAM49B), thus aggravating hepatic I/R injury. Here, we found that miR-22 was upregulated while FAM49B was reduced in hepatic I/R injury. Inhibition of miR-22 in vitro was able to intensify expression of FAM49B, thus reducing phosphorylation of inhibitors of nuclear factor kappa-B kinase (IKK) and downstream pro-inflammatory proteins. A dual luciferase reporter assay indicated that miR-22 directly targeted FAM49B. Remission of hepatic pathologic alterations, Apoptosis, and release of cytokines derived from constraints of miR-22 were abolished in vivo by repressing FAM49B. Further interference of Ras-related C3 botulinum toxin substrate 1 (Rac1) reversed the function of FAM49B inhibition, thus achieving anti-inflammatory consequences.

Keywords
FAM49B; IKK; Inflammation; Ischemia/reperfusion injury; MiR-22.
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