Platelet-derived microvesicles drive vascular smooth muscle cell migration via forming podosomes and promoting matrix metalloproteinase-9 activity  

作　　者：He Ren Jiahe Chen Kai Huang Ying-Xin Qi 

机构地区：[1]Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education,School of Biological Science and Medical Engineering,Beihang University,Beijing,100083,China [2]Institute of Mechanobiology&Medical Engineering,School of Life Sciences&Biotechnology,Shanghai Jiao Tong University,800 Dongchuan Road,Minhang,Shanghai,200240,China

出　　处：《Mechanobiology in Medicine》2023年第1期44-50,共7页力学生物学与医学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China[grant numbers 12032003 and 12102261].

摘　　要：We have shown that platelet-derived microvesicles(PMVs)induce abnormal proliferation,migration,and energy metabolism of vascular smooth muscle cells(VSMCs)after vascular intimal injury.Here,we examined a novel role of podosome in mediating matrix metalloproteinase-9(MMP-9)dependent VSMC migration induced by plateletderived microvesicles(PMVs).VSMCs were isolated from the thoracic aortas of male Sprague Dawley(SD)rats and identified with immunofluorescent staining.Blood samples were collected from SD Rats,the platelets were isolated with density gradient centrifugation from the blood samples and activated by collagen I.Intriguingly,proteins expressed in platelets were found to participate in the positive regulation of podosome assembly using GO analysis by DAVID,and most of the proteins were found in extracellular exosomes.Of note,activated platelets indirectly induced VSMC migration via releasing PMVs which was verified using platelets and VSMCs transwell coculture system.Besides,podosome,an invasive protrusion to mediate extracellular matrix(ECM)remodeling,was formed in VSMCs to induce cell migration.Furthermore,MMP-9 activity detected by gelatin zymography was used to verify the function of the podosome in ECM remodeling.The result indicated that MMP-9 activity was robustly activated in VSMCs to implement the function of the podosome.In addition,gelatin degradation was detected in intact VSMCs using a gelatin degradation assay after co-culture with platelets.Taken together,our data reveal a novel mechanism that PMVs promote VSMC migration via forming podosomes and inducing MMP-9 activity.

关 键 词：Platelet-derived microvesicles(PMVs) Vascular smooth muscle cells(VSMCs) PODOSOME Matrix metalloproteinase-9(MMP-9) Migration 

分 类 号：R54[医药卫生—心血管疾病]