Clinical Microbiology: Open Access

Matrix metallopeptidase-14 and transforming growth factor-β1 are involved in migration and recruitment of mesenchymal stem cells in neointima formation after vascular injury

Joint Event on 25^th Asia Pacific Biotechnology Congress & 3^rd International Conference on Medical and Clinical Microbiology

May 01-02, 2019 Kyoto, Japan

Lijuan Pang, Shan Jin, Lu Zhang, Hongrun Zhou, Chengyan Wang, Dongdong Chen, Kunming Sun and Cuilei Wei

Shihezi University School of Medicine, China

Scientific Tracks Abstracts: Clin Microbiol

Abstract:

Introduction & Objective: Restenosis or occlusion after vascular surgery is ascribed to intimal hyperplasia. The release of latent Transforming Growth Factor-β1 (TGF-β1) from Latent TGF-binding Protein (LTBP) by Matrix Metallopeptidase-14 (MMP-14) proteolysis was demonstrated, which contributed to neointima formation, but the relationship between MMP-14 and activated TGF-β1 in the process of restenosis has yet to be explored.

Method: In this study, the relationship was studied both in vitro and in vivo. Common carotid artery balloon injured model of rats were built. Rats were assigned to vehicle-, SB431542 (SB)-, recombinant human (rh) TGF-β1- or MMP-14 inhibitortreated groups and examined at various time points after arterial injury for expression of TGF-β1/Smad signaling pathway components, MMP-14 and MSCs markers. In vitro, BMSCs (Bone Mesenchymal Stem Cells) and VSMCs (Vascular Smooth Muscle Cells) were cultured, then transfected with MMP-14 plasmid and treated with MMP-14 inhibitor. The expressions of MMP-14 and TGF-β1 in thoracic aorta of normal SD rats with arterial injury in Conditioned Medium (CM) were increased using ELISA. CO-IP assay detected the relationship between MMP-14 and TGF-β1

Results: It can be obviously observed neointima at 7 days, 14 days, 21 days, 28 days after arterial injury. The increase in TGF-β1 levels was preceded by the activation of MMP-14. We found that the increase in the improvement on TGF-β1/Smad signaling was consistent with the elevation of TGF-β1 levels and MSCs accumulated at the lumen side of neointima. However, intimal hyperplasia was reduced in SB431542 (SB)- or MMP-14 inhibitor-treated groups. MMP-14 inhibitor administration decreased the expression of TGF-β1/Smad pathway proteins. Nestin and CD29 expression were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-β1 administration. CO-IP assay also detected the relationship between MMP-14 and TGF-β1. In vitro, after transfecting with MMP-14 plasmid, TGF-β1 signaling pathway proteins were also increased, the ability of proliferation and migration were enhanced in BMSCs and VSMCs, but it has no obvious effect on proliferation of VSMCs. Inhibition of MMP-14 can attenuate the migration of BMSCs and VSMCs, and inhibit the proliferation of BMSCs.

Conclusion: MMP-14 participated in the process of neointima formation after vascular injury by activating TGF-β1 signaling pathway to regulated BMSCs and VSMCs.

Biography :

Lijuan Pang has completed her PhD at Tongji Medical College, Huazhong University of Science and Technology. She is currently working as a Professor in Department of Pathology, Shihezi University School of Medicine. She has published more than 50 academic papers and 28 articles published in the SCI journals as first author or correspondent author. Her current research is focused on molecular diagnostics of tumors, the role of cancer stem cells and exosomes in liquid biopsy and tumor pathogenesis and the potential application of stem cells in vascular injury and repair.

E-mail: ocean123456@163.com