Resistin-like molecule beta augments phenotypic modulation of human aortic smooth muscle cell triggered by high glucose
- 1 January 2021
- journal article
- research article
- Published by Japan Endocrine Society in Endocrine Journal
- Vol. 68 (4), 461-468
- https://doi.org/10.1507/endocrj.ej20-0343
Abstract
Vascular muscle cells (VSMCs) participate in the pathophysiology of atherosclerosis. Resistin-like molecule beta (Relmβ) contributes to atherosclerosis development by activating macrophage. This study aims to investigate whether Relmβ regulates VSMC phenotypic modulation under high glucose environment. Human aortic vascular smooth muscle cells were cultured and treated with Relmβ in the presence or absence of high glucose. VSMC phenotypic modulation was assessed by expression of related markers. The migration of VSMCs was detected by wound healing assay and transwell assay. The proliferation of VSMCs was measured using CCK-8 assay. In this study, we observed that Relmβ modulated VSMC phenotypic modulation by down-regulating expression of smooth muscle α-actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), and calponin while up-regulating expression of osteopontin (OPN). Relmβ increased the expression of inflammatory genes in VSMCs. Relmβ also augmented VSMCs migration as well as proliferation. It is worth noting that all the effects of VSMCs were enhanced upon high glucose stimulation. The phosphorylation levels of p38MAPK and ERK1/2 were increased by co-treatment with Relmβ and high glucose. The p38 MAPK pathway inhibitor RWJ64809 and pERK1/2 inhibitor PD98059 significantly inhibited the proliferation of VSMCs induced by Relmβ and high glucose. Our results provide evidence that Relmβ augments phenotypic modulation and migration of human aortic smooth muscle cell induced by high glucose. Relmβ might be a potential target for treatment of atherosclerosis induced by hyperglycemia.Keywords
This publication has 27 references indexed in Scilit:
- Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis DevelopmentArteriosclerosis, Thrombosis, and Vascular Biology, 2013
- Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interfaceProceedings of the National Academy of Sciences of the United States of America, 2008
- Enhanced Expression of Resistin-like Molecule Beta in Human Colon Cancer and Its Clinical SignificanceDigestive Diseases and Sciences, 2008
- Natural History of Cardiovascular Disease in Patients With DiabetesDiabetes Care, 2008
- Human RELMβ is a mitogenic factor in lung cells and induced in hypoxiaFEBS Letters, 2006
- Thematic Review Series: The Immune System and Atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular diseaseJournal of Lipid Research, 2005
- Serum concentrations of resistin-like molecules β and γ are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrowDiabetologia, 2005
- Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific proteinGastroenterology, 2003
- A family of tissue-specific resistin-like moleculesProceedings of the National Academy of Sciences of the United States of America, 2001
- Vascular smooth muscle cell proliferation and its therapeutic modulation in hypertensionAmerican Heart Journal, 1991