title: Effect of TGF-β1 on the Migration and Recruitment of Mesenchymal Stem Cells after Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14.
abstract: Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-β1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury, and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-β1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-β1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-β1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29, and Sca1(+)CD29(+)CD11b/c(-)CD45(-). Intimal hyperplasia was reduced in SB- and rhTGF-β1-treated rats. The expression of TGF-β1, TGF-β1RI, and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF-β1 administration decreased the expression of TGF-β1/Smad pathway proteins, except for TGF-β1RI. Nestin and CD29 expression and the number of Sca1(+)CD29(+)CD11b(-)CD45(-) cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-β1 administration. These results suggest that TGF-β1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling.
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Cuilei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Shihezi University School of Medicine, 45 North 3rd Road, Shihezi, Xinjiang 832008, China.
authors.forename: Juncang
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Shihezi University School of Medicine, 45 North 3rd Road, Shihezi, Xinjiang 832008, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Public Health, Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Lianghai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D002465:Cell Movement; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D066253:Vascular Remodeling; D057772:Vascular System Injuries / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D053511:Matrix Metalloproteinase 14