Int J Med Sci 2019; 16(8):1149-1156. doi:10.7150/ijms.34749

Research Paper

The phenotype of vascular smooth muscle cells co-cultured with endothelial cells is modulated by PDGFR-β/IQGAP1 signaling in LPS-induced intravascular injury

Xia Zheng1✉*, Xiaotong Hu2*, Wang Zhang1

1. Department of Critical Care Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310003, P.R. China.
2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, P.R. China.
*Co-first author

Abstract

Background Sepsis, a leading cause of death in intensive care units, is generally associated with vascular dysfunction. However, its pathophysiological process has not been fully clarified, lacking in-depth knowledge of its pathophysiological process may hinder the improvement of diagnosis and therapy for sepsis. Hence, as the key parts of the vascular wall, the interaction between endothelial cells (ECs) and smooth muscle cells (SMCs) under septic situation need to be further studied.

Methods ECs and SMCs were co-cultured using Transwell plates. Lipopolysaccharide (LPS) was used to induce sepsis. A scratch-wound assay was used to assess cell migration, and western blotting was used to assess the level of redifferentiation of SMCs as well as the expression of PDGFR-β and IQGAP1.

Results Co-culture with ECs reduced the redifferentiation of SMCs induced by LPS (10 μg/ml), which was characterized by increased migration ability and decreased expression of contractile proteins (e.g., SM22 and α-SMA). The production of TNF-α could decrease the level of PDGFR-β in SMCs. Treatment of SMCs with the PDGFR-β inhibitor imatinib (5 μM) was able to counteract LPS-induced SMC redifferentiation and reduce IQGAP1 protein expression, especially when SMCs were co-cultured with ECs.

Conclusion The phenotype of vascular SMCs co-cultured with ECs was modulated by IQGAP1 through the PDGFR-β pathway, which may lead to vascular remodeling and homeostasis in LPS-induced intravascular injury. This pathway could be a novel target for the treatment of vascular damage.

Keywords: sepsis, endothelial cells, smooth muscle cells, phenotype, Intravascular Injury.

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How to cite this article:
Zheng X, Hu X, Zhang W. The phenotype of vascular smooth muscle cells co-cultured with endothelial cells is modulated by PDGFR-β/IQGAP1 signaling in LPS-induced intravascular injury. Int J Med Sci 2019; 16(8):1149-1156. doi:10.7150/ijms.34749. Available from http://www.medsci.org/v16p1149.htm