Humanin prevents high glucose-induced monocyte adhesion to endothelial cells by targeting KLF2

Molecular Immunology
Xiaohui WangYunjun He

Abstract

Endothelial dysfunction and vascular complications induced by hyperglycemia play an important role in the pathological development of atherosclerosis in diabetes. Humanin, a 24-amino acid mitochondria-derived polypeptide, has displayed its cytoprotective effects in diverse cell types and tissues. In the current study, we aimed to characterize the effects of humanin on high glucose-induced endothelial dysfunction. Firstly, we found that humanin treatment induced the expression of Krüppel-like factor 2 (KLF2), an essential transcriptional regulator of endothelial function, at the transcriptional level in human umbilical vein endothelial cells (HUVECs). Additionally, our results indicate that humanin treatment regulated the expression of KLF2 target genes such as endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1). Evidence demonstrated that the effects of humanin on KLF2 expression was mediated by the phosphorylation of extracellular signal regulated kinase 5 (ERK5). Furthermore, humanin restored high glucose-induced reduction of KLF2 expression. We also showed that humanin significantly reduced the expression of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. Notably, humanin treatment markedly prevented ...Continue Reading

Citations

Aug 15, 2020·Frontiers in Immunology·Gholamreza DaryaborKurosh Kalantar
Mar 5, 2020·Cellular and Molecular Life Sciences : CMLS·Jialong YanLinxi Chen
Feb 23, 2020·Biochemistry. Biokhimii︠a︡·K T Turpaev
Jul 19, 2020·Archives of Cardiovascular Diseases·Luc RochetteCatherine Vergely
Jun 4, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Meng-Yuan ShenYing Xie
Aug 28, 2021·International Journal of Molecular Sciences·Siarhei A DabravolskiAlexander N Orekhov

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