KLF5 overexpression attenuates cardiomyocyte inflammation induced by oxygen-glucose deprivation/reperfusion through the PPARγ/PGC-1α/TNF-α signaling pathway

The primary physiological function of Kruppel-like zinc-finger transcription factor (KLF5) is the regulation of cardiovascular remodeling. Vascular remodeling is closely related to the amelioration of various ischemic diseases. However, the underlying correlation of KLF5 and ischemia is not clear. In this study, we aim to investigate the role of KLF5 in myocardial ischemia reperfusion (IR) injury and the potential mechanisms involved. Cultured H9C2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/Rep) to mimic myocardial IR injury in vivo. Expressions of KLF5 and PPAR gamma were distinctly inhibited, and PGC-1 alpha expression was activated at 24 h after myocardial OGD/Rep injury. After myocardial OGD/Rep injury, we found that KLF5 overexpression down-regulated levels of TNF-alpha, IL-1 beta, IL-6 and IL-8. Through the analysis of lactate dehydrogenase (LDH) release, we demonstrate that KLF5 overexpression reduced the release of OGD/Rep-induced LDH. KLF5 overexpression significantly enhanced cell activity and decreased cell apoptosis during OGD/Rep injury. Compared with the OGD/Rep group, cells overexpressing KLF5 showed anti-apoptotic effects, such as decreased expression of Bax and cleaved caspase-3 as well as increased Bcl-2 expression. KLF5 overexpression activated PPARg, a protein involved in OGD/Rep injury, and increased levels of PGC-1 alpha, while TNF-alpha xpression was remarkably inhibited. In addition, GW9662, a PPAR gamma receptor antagonist, reversed the expression of PPAR gamma/PGC-1 alpha/TNF-alpha and cell activity induced by KLF5 overexpression. The effects of KLF5 overexpression on PPAR gamma/PGC-1 alpha/TNF-alpha and cell activity were abolished by co-treatment with GW9662. Taken together, these results suggest that KLF5 can efficiently alleviate OGD/Rep-induced myocardial injury, perhaps through regulation of the PPAR gamma/PGC-1 alpha/TNF-alpha pathway. (C) 2016 Elsevier Masson SAS. All rights reserved.