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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The development of atherosclerotic cardiovascular disease isassociated with the phenotypic switching of vascular smoothmuscle cells (SMCs) from a contractile to a synthetic state,leading to cell migration and proliferation. Platelet‑derivedgrowth factor‑BB (PDGF‑BB) modulates this de-differentiationby initiating a number of biological processes. In this study,we show that gene expression of hyaluronic acid (HA) andproteoglycan link protein 1 (HAPLN1) was upregulated duringdifferentiation of human aortic SMCs (HASMCs) into a contractilestate, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatmentof HASMCs with full-length recombinant human HAPLN1(rhHAPLN1) significantly reversed PDGF-BB-induced decreasein the protein levels of contractile markers (SM22α, α-SMA,calponin, and SM-MHC), and inhibited the proliferation andmigration of HASMCs induced by PDGF-BB. Furthermore, ourresults show that rhHAPLN1 significantly inhibited thephosphorylation of FAK, AKT, STAT3, p38 MAPK and Rafmediated by the binding of PDGF-BB to PDGFRβ. Together,these results indicated that rhHAPLN1 can suppress thePDGF-BB-stimulated phenotypic switching and subsequentde-differentiation of HASMCs, highlighting its potential as anovel therapeutic target for atherosclerosis and other vasculardiseases.
Abstract
The development of atherosclerotic cardiovascular disease isassociated with the phenotypic switching of vascular smoothmuscle cells (SMCs) from a contractile to a synthetic state,leading to cell migration and proliferation. Platelet‑derivedgrowth factor‑BB (PDGF‑BB) modulates this de-differentiationby initiating a number of biological processes. In this study,we show that gene expression of hyaluronic acid (HA) andproteoglycan link protein 1 (HAPLN1) was upregulated duringdifferentiation of human aortic SMCs (HASMCs) into a contractilestate, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatmentof HASMCs with full-length recombinant human HAPLN1(rhHAPLN1) significantly reversed PDGF-BB-induced decreasein the protein levels of contractile markers (SM22α, α-SMA,calponin, and SM-MHC), and inhibited the proliferation andmigration of HASMCs induced by PDGF-BB. Furthermore, ourresults show that rhHAPLN1 significantly inhibited thephosphorylation of FAK, AKT, STAT3, p38 MAPK and Rafmediated by the binding of PDGF-BB to PDGFRβ. Together,these results indicated that rhHAPLN1 can suppress thePDGF-BB-stimulated phenotypic switching and subsequentde-differentiation of HASMCs, highlighting its potential as anovel therapeutic target for atherosclerosis and other vasculardiseases.
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