MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway

Abstract

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.

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

“…Protein extraction and quantification procedure of CRYAB (CST, Shanghai, China), p-IκBα, IκBα, S6K, 4E-BP (Santa Cruz Bio, Santa Cruz, USA), IKKα, IKKβ, p-p65, p65, IKK, p-IKK, Arg-1, TGF-β1, β-actin, and p-4E-BP (Beyotime, Shanghai, China), IL-1β (Wanleibio, Shanghai, China), NIK, p52, p-IKKα, p-IKKβ (Invitrogen, CA, USA), p-Akt1, Akt1, p-Akt2, Akt2, p-mTOR, mTOR, and p-S6K (Abcam, Cambridge, UK) was consistent with our previous researches 6,46 . Primary antibody dilutions for Western blot are listed in Table 2.…”

“…Liver IRI model was constructed in accordance with our previous studies 6,47 . Reperfusion for 1, 3, 6, and 9 h was performed after 1-h ischemia with vascular clamping as previously depicted.…”

“…However, the whole molecular mechanism of hepatic IRI remains to be unfolded 3,4 . Occurrence of inflammation induced by NF-κB plays a critical part among these disparate pathogeneses [5][6][7] . While activation of NF-κB canonical pathway results in release of inflammatory cytokines with requirement of IKKβ phosphorylation, noncanonical NF-κB demands the codependence of IKKα and NF-κBinducing kinase (NIK) [8][9][10][11] .…”

SUMO2/3 participates in regulating the protective effect of propofol on human umbilical vein endothelial cells

“…I/R injury is one of the main causes of tissue and cell injury in clinical operation [24]. It has been discovered that propofol can affect the biological functions of tissues and cells through different mechanisms, especially inhibiting I/R-induced cell injury.…”

Roles of TRAFs in Ischemia-Reperfusion Injury

“…Moreover, aloin and N-Acetylserotonin (NAS) were respectively involved in the regulating of liver and intestinal IRI by targeting TRAF6 ( Du et al, 2019 ; Sukhotnik et al, 2019 ; Figure 4 ), which provides targets for clinical treatment of liver and intestinal IRI-related diseases. In addition, miRNA-based treatments for IRI are very popular in recent years ( Huang Z. et al, 2019 ; Liang et al, 2019 ). Many studies have shown that the increased expression of miR-146a could inhibit TRAF6 to alleviate IRI of various organs, including the myocardia, kidney, intestine, and liver ( Chen et al, 2013 ; Wang X. et al, 2013 ; Jiang et al, 2014 ; Dai et al, 2016 ; He et al, 2018 ).…”