Chemokine-Like Receptor 1 Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells

Abstract

BackgroundWe aimed to explore how chemokine-like receptor 1 (CMKLR1) influences the proliferation and migration of vascular smooth muscle cells (VSMCs).Material/MethodsNormal VSMCs, negative control VSMCs interfered by CMKLR1 gene, and VSMCs with stable knockdown of CMKLR1 gene were divided into the control group, PDGF group, negative-shRNA group, and CMKLR1-shRNA group. Both cell number counting and BrdU incorporation assays were employed to investigate the proliferation status of VSMCs. Transwell migration assay was used to measure the migration status of VSMCs. Inflammation markers, including cytokines IL-1β, IL-6, TNF-α, and chemokines MCP-1 in VSMCs, were detected by real-time quantitative RT-PCR. Western blotting assay was used to detect protein expressions of the MAPK pathway in VSMCs.ResultsThe number of VSMCs and the OD value of BrdU in PDGF group were significantly higher than those in the control group (both P<0.05). Compared with the control and negative-shRNA group, the CMKLR1-shRNA group exhibited significantly reduced VSMCs number and BrdU OD value (both P<0.05). Transwell migration assay indicated that PDGF-BB promoted whereas CMKLR1-shRNA inhibited the migration of VSMCs. The expression of IL-1β, IL-6, TNF-α, and MCP-1 were up-regulated in the PDGF group but down-regulated in the CMKLR1-shRNA group. Compared with normal VSMCs, the protein level of p-ERK1/2 was up-regulated in VSMCs treated with PDGF-BB, while it was down-regulated in the CMKLR1-shRNA group.ConclusionsCMKLR1 exacerbated the proliferation and migration of VSMCs by activating ERK1/2.

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

“…investigation revealed that knockdown of chemerin receptor, CMKRL1, inhibited proliferation and migration of vascular SMCs (Liu et al, 2016), suggesting main chemerin-induced activity through CMKLR1. These apparent discrepant results may result from variable cell proliferation protocol and SMC origin, but also to lower concentrations of chemerin compared to those used in previously cited studies.…”

Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE−/− Mice

“…In the isolated rat thoracic aorta, CMKLR1 agonist chemerin-9 caused arterial contraction in a dose-dependent manner, while CMKLR1 antagonist CCX832 inhibited phenylephrine-induced vasoconstriction [37]. Our previous study indicated that the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) was inhibited by knockdown of CMKLR1 [18]. Our current data suggested that chemerin stimulated the progression of atherosclerosis by promoting p38 MAPK phosphorylation and NF- κ Bp65 expression.…”

“…In a previous study, we found that circulating chemerin levels increased after carotid balloon injury, and knockdown of chemerin significantly inhibited the VSMCs proliferation in vitro as well as prohibited carotid neointimal hyperplasia in vivo after angioplasty [17]. Further investigation revealed that knockdown of chemerin receptor, chemokine-like receptor 1 (CMKLR1), inhibited the proliferation and migration of VSMCs [18].…”

The role of chemerin and chemerin receptors during acute inflammation

“…In an adoptive transfer study of the model, they found that wild type bone marrow reconstitution into ChemR23 -/mice, augmented the inflammatory response [178]. As stated in the Introduction 4.1.1, there are large amount of nonleukocyte cell types which do express the chemerin receptors, including adipocytes, vascular smooth muscle cells, endothelial and lung epithelial cells [263,266,218,176]. 123…”

“…vascular smooth muscle cells [124,266]. Finally, ChemR23 receptor influences the proliferation and migration of vascular smooth muscle cells [124,266].…”