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Inhibition of microRNA-297 alleviates THLE-2 cell injury induced by hypoxia/reoxygenation by inhibiting NLRP3 inflammasome activation via sirtuin 3
- Source :
- Canadian Journal of Physiology and Pharmacology. 100:125-133
- Publication Year :
- 2022
- Publisher :
- Canadian Science Publishing, 2022.
-
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.
- Subjects :
- SIRT3
Inflammasomes
Physiology
Cell
Apoptosis
chemistry.chemical_compound
Sirtuin 3
Physiology (medical)
NLR Family, Pyrin Domain-Containing 3 Protein
microRNA
medicine
Humans
Antagomir
Cells, Cultured
Cell Proliferation
bcl-2-Associated X Protein
Pharmacology
TUNEL assay
Interleukin-6
Cell growth
Liver Diseases
Antagomirs
General Medicine
MicroRNAs
IκBα
medicine.anatomical_structure
chemistry
Reperfusion Injury
Hepatocytes
Cancer research
Subjects
Details
- ISSN :
- 12057541 and 00084212
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Physiology and Pharmacology
- Accession number :
- edsair.doi.dedup.....00faf9dd8eb6bde201e80fa265340060