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

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.

Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing

“…It has been reported that CTEPH endothelial cells can exhibit pro-fibrotic and pro-inflammatory phenotypes, as demonstrated by the expression of genes (COL1A1 and COL3A1) involved in extracellular matrix production and fibril organization [20]. In addition, PDGF is a potent mitogen for cells of mesenchymal origin, such as fibroblasts and smooth muscle cells [21]. Previous studies have revealed that smooth muscle 22 (SM22) and α-smooth muscle actin (α-SMA) are major marker genes of smooth muscle cells [22].…”

Osteopontin Promotes Trophoblast Invasion in the Smooth Muscle Cell-Endothelial Co-Culture At Least Via Targeting Integrin αvβ3

“…The SMC-EC co-culturing systems have been recently applied in the investigation of cardiovascular diseases 18 , 19 . Zheng et al found that the phenotype of vascular SMCs co-cultured with endothelial cells is modulated by platelet-derived growth factor receptor beta/IQ motif containing GTPase activating protein 1 signaling in lipopolysaccharides-induced intravascular injury 20 . In the aspect of preeclampsia studies, Dunk et al developed an in vitro co-culture system in which first trimester villous explants are cultured at low oxygen tension in contact with 2-mm 2 sections of decidua parietalis from the same patient 21 .…”