Hypoxia Triggers SENP1 (Sentrin-Specific Protease 1) Modulation of KLF15 (Kruppel-Like Factor 15) and Transcriptional Regulation of Arg2 (Arginase 2) in Pulmonary Endothelium.

Arteriosclerosis, Thrombosis, and Vascular Biology
Deepesh PandeyLewis H Romer

Abstract

KLF15 (Kruppel-like factor 15) has recently been shown to suppress activation of proinflammatory processes that contribute to atherogenesis in vascular smooth muscle, however, the role of KLF15 in vascular endothelial function is unknown. Arginase mediates inflammatory vasculopathy and vascular injury in pulmonary hypertension. Here, we tested the hypothesis that KLF15 is a critical regulator of hypoxia-induced Arg2 (arginase 2) transcription in human pulmonary microvascular endothelial cells (HPMEC). Quiescent HPMEC express ample amounts of full-length KLF15. HPMECs exposed to 24 hours of hypoxia exhibited a marked decrease in KLF15 protein levels and a reciprocal increase in Arg2 protein and mRNA. Chromatin immunoprecipitation indicated direct binding of KLF15 to the Arg2 promoter, which was relieved with HPMEC exposure to hypoxia. Furthermore, overexpression of KLF15 in HPMEC reversed hypoxia-induced augmentation of Arg2 abundance and arginase activity and rescued nitric oxide (NO) production. Ectopic KLF15 also reversed hypoxia-induced endothelium-mediated vasodilatation in isolated rat pulmonary artery rings. Mechanisms by which hypoxia regulates KLF15 abundance, stability, and compartmentalization to the nucleus in HPMEC ...Continue Reading

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Citations

Apr 25, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Jun ChengYan Yang
Dec 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Feb 19, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuan-Yuan LuPing-Jin Gao
May 28, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Ying ShaoXiaofeng Yang
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Oct 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Zekun PengMiao Wang
Apr 18, 2019·Developmental Neuroscience·Jana KrystofovaDonna Ferriero

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