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Biophysically stressed vascular smooth muscle cells express MCP-1 via a PDGFR-β-HMGB1 signaling pathway

  • Ji Won Kim (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Ju Yeon Kim (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Hee Eun Bae (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Chi Dae Kim (Department of Pharmacology, School of Medicine, Pusan National University)
  • 투고 : 2024.02.29
  • 심사 : 2024.04.02
  • 발행 : 2024.09.01

초록

Vascular smooth muscle cells (VSMCs) under biophysical stress play an active role in the progression of vascular inflammation, but the precise mechanisms are unclear. This study examined the cellular expression of monocyte chemoattractant protein 1 (MCP-1) and its related mechanisms using cultured rat aortic VSMCs stimulated with mechanical stretch (MS, equibiaxial cyclic stretch, 60 cycles/min). When the cells were stimulated with 10% MS, MCP-1 expression was markedly increased compared to those in the cells stimulated with low MS intensity (3% or 5%). An enzyme-linked immunosorbent assay revealed an increase in HMGB1 released into culture media from the cells stimulated with 10% MS compared to those stimulated with 3% MS. A pretreatment with glycyrrhizin, a HMGB1 inhibitor, resulted in the marked attenuation of MCP-1 expression in the cells stimulated with 10% MS, suggesting a key role of HMGB1 on MCP-1 expression. Western blot analysis revealed higher PDGFR-α and PDGFR-β expression in the cells stimulated with 10% MS than 3% MS-stimulated cells. In the cells deficient of PDGFR-β using siRNA, but not PDGFR-α, HMGB1 released into culture media was significantly attenuated in the 10% MS-stimulated cells. Similarly, MCP-1 expression induced in 10% MS-stimulated cells was also attenuated in cells deficient of PDGFR-β. Overall, the PDGFR-β signaling plays a pivotal role in the increased expression of MCP-1 in VSMCs stressed with 10% MS. Therefore, targeting PDGFR-β signaling in VSMCs might be a promising therapeutic strategy for vascular complications in the vasculatures under excessive biophysical stress.

키워드

과제정보

This study was supported by a 2-Year Research Grant of Pusan National University, Republic of Korea.

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