Hyaluronic acid and proteoglycan link protein 1 suppresses platelet-derived growth factor-BB-induced proliferation, migration, and phenotypic switching of vascular smooth muscle cells

Hyaluronic acid and proteoglycan platelet -derived growth factor-BB migration, and phenotypic switching muscle cells Dan Zhou1,2, Hae Chan Ha1, Goowon Yang2, Ji Min Jang1,2, Bo & Dae Kyong Kim1,2,* 1Department of Environmental & Health Chemistry, College of Pharmacy, Institute, HaplnScience Inc., Seongnam 13494, Korea 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 dedifferentiation. 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 (SM22 alpha, alpha-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 PDGFR beta. 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. [BMB Reports 2023; 56(8): 445-450]