Affiliation:
1. Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, P.R. China.
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, P.R. China.
Abstract
It has been acknowledged that microRNAs (miRNAs/miRs) assume a critical role in hypoxia/reoxygenation (H/R) – induced hepatocyte injury. Therefore, cell experiments were performed in this study to investigate the mechanism of miR-297 in H/R-induced hepatocyte injury with the involvement of sirtuin 3 (SIRT3) and NOD-like receptor pyrin domain containing 3 (NLRP3). Initially, transformed human liver epithelial-2 (THLE-2) cells were utilized for H/R challenge. After miR-297 antagomir and NLRP3 adenovirus vector delivery, THLE-2 cell proliferation and apoptosis were measured by MTT, EdU, and TUNEL assays, respectively. Enzyme-linked immunosorbent assay was conducted to evaluate the levels of apoptosis-related indicators (Bax and Bcl-2) and inflammation-related indicators (interleukin 6 (IL-6) and IL-10), Western blot analysis to detect NLRP3, and cleaved caspase-1 expression. The binding relation between miR-297 and SIRT3 was examined using dual-luciferase assay. The results showed that miR-297 antagomir repressed the apoptosis and inflammation induced by H/R treatment in THLE-2 cells. Mechanistically, miR-297 antagomir diminished the extent of IκBα and nuclear factor-kappa B (NF-κB) phosphorylation and NLRP3 activation in H/R-induced THLE-2 cells by targeting SIRT3. Furthermore, NLRP3 overexpression normalized the promoting effects of miR-297 antagomir on proliferation and its inhibitory effects on apoptosis and inflammation in H/R-induced THLE-2 cells. In summary, our results elucidated that miR-297 antagomir repressed H/R-induced THLE-2 cell injury via SIRT3 promotion and NLRP3 inactivation.
Publisher
Canadian Science Publishing
Subject
Physiology (medical),Pharmacology,General Medicine,Physiology
Cited by
9 articles.
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