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KMID : 0624620230560080445
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BMB Reports
2023 Volume.56 No. 8 p.445 ~ p.450
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Hyaluronic acid and proteoglycan link protein 1 suppresses platelet-derived growth factor-BB-induced proliferation, migration, and phenotypic switching of vascular smooth muscle cells
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Dan Zhou
Ha Hae-Chan
Yang Goo-Won
Jang Ji-Min
Park Bo-Kyung
Zhicheng Fu
Shin In-Chul
Kim Dae-Kyong
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Abstract
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The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet?derived growth factor?BB (PDGF?BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced de-differentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.
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KEYWORD
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HAPLN1, HASMC, PDGF-BB, Phenotypic switch
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