title: TGF-β1/Smad signaling, MMP-14, and MSC markers in arterial injury: discovery of the molecular basis of restenosis.
abstract: Transforming growth factor (TGF)-β1 has been suggested to be involved in the recruitment of mesenchymal stem cells (MSCs) following arterial injury, but the role of downstream signaling and the contribution of the recruited MSCs are still unknown. The release of latent 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. In this study, we observed the change in expression and distribution of TGF-β1/Smad signaling pathway proteins, MMP-14, and MSC markers in the process of neointima formation using a rat model for balloon-induced carotid artery injury. We found that the increase in downstream Smad signaling was consistent with the elevation of TGF-β1 levels and MSCs accumulated at the lumen side of neointima. Furthermore, the activation of MMP-14 in the injured artery was preceded by the increase in TGF-β1 levels. Herein, we conclude that MMP-14 induces an elevation in the levels of TGF-β1/Smad signaling proteins in injured arteries, and that MSCs are recruited by TGF-β1/Smad signaling and MMP-14, possibly differentiating into vascular smooth muscle cell (VSMC)-like cells and VSMC via modulation of TGF-β1/Smads signaling and MMP-14.
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine 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 Shihezi, Xinjiang 832002, China.
authors.forename: Cuilei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Juncang
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine 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 Shihezi, Xinjiang 832002, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine 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 Shihezi, Xinjiang 832002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine 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 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 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 Shihezi, Xinjiang 832002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D053511:Matrix Metalloproteinase 14
keywords: MMP-14; TGF-β1/Smad signaling pathway; balloon injury; mesenchymal stem cells; restenosis