Pioglitazone alleviates oxygen and glucose deprivation-induced injury by up-regulation of miR-454 in H9c2 cells
Authors: Qian Zhang
Nianzi Sun
Chengwei Zou
Lin Yang
Journal: Iranian journal of basic medical sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ERK/MAPK; MicroRNA-454; Oxygen glucose deprivation Pioglitazone; PI3K/AKT.
Affiliations: Shandong University, Jinan 250100, Shangdong, China., Department of Cardiac Surgery, Linyi People's Hospital, Linyi 276000, Shandong, China., Department of Equipment, Linyi People's Hospital, Linyi 276000, Shandong, China., Department of Cardiac Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.

Abstract:  Objectives: Pioglitazone, an anti-diabetic agent, has been widely used to treat type II diabetes. However, the effect of pioglitazone on myocardial ischemia reperfusion injury (MIRI) is still unclear. Herein, the objective of this study is to learn about the regulation and mechanism of pioglitazone effects on oxygen glucose deprivation (OGD)-induced myocardial cell injury. Materials and methods: A cellular injury model of OGD-treated H9c2 cells in vitro was constructed to simulate ischemic/reperfusion (I/R) injury. Then, various concentrations of pioglitazone (0, 2.5, 5, 7.5 and 10 μM) were used for the treatment of H9c2 cells, and CCK-8, flow cytometry and western blot assays were performed to examine cell viability, apoptosis, and the protein levels of factors involved in cell cycle and apoptosis in OGD-treated cells. MiR-454 inhibitor was used to suppress miR-454 expression, and whether miR-454 was involved in regulating OGD-induced cell injury was studied. Two key signal pathways were examined to uncover the underlying mechanism. Results: OGD reduced cell proliferation and induced apoptosis in H9c2 cells (P&lt;0.05, P&lt;0.01 or P&lt; 0.001). OGD-induced injury was significantly attenuated by pioglitazone at the concentration of 5 μM. Additionally, pioglitazone significantly up-regulated miR-454 expression in OGD-injured cells (P&lt; 0.05 or P&lt; 0.01). MiR-454 suppression declined the protective effect of pioglitazone on OGD-injured H9c2 cells (P&lt;0.05 or P&lt; 0.01). Besides, pioglitazone activated PI3K/AKT and ERK/MAPK pathways via up-regulating miR-454. Conclusion: Pioglitazone protected H9c2 cells against OGD-induced injury through up-regulating miR-454, indicating a novel therapeutic strategy for treatment of MIRI. 

Retracted: No

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 ,