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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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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

  • Dan Zhou (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Hae Chan Ha (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Goowon Yang (HaplnScience Research Institute, HaplnScience Inc.) ;
  • Ji Min Jang (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Bo Kyung Park (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Bo Kyung Park (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • In Chul Shin (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Dae Kyong Kim (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University)
  • Received : 2023.05.25
  • Accepted : 2023.06.26
  • Published : 2023.08.31
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Abstract

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 (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.

Keywords

Acknowledgement

This research was supported by the Chung-Ang University Young Scientist Scholarship in 2017, and the grant from the National Research Foundation of Korea (NRF-2017M3A9D8048414), funded by the Korean government (Ministry of Science and ICT).

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