title: MMP-14 promotes VSMC migration via up-regulating CD44 expression in cardiac allograft vasculopathy.
abstract: Cardiac allograft vasculopathy (CAV) was the leading cause of late death in heart transplantation recipients. Matrix metalloproteinase-14 (MMP-14), as a member of the MMPs family, has been reported to play a vital role in coronary vascular lesions of allotransplanted hearts. However, concrete mechanism is still unclear. Herein, we showed that the expression of MMP-14 was different between isografts and allografts. Interestingly, we found MMP-14 could interact with CD44 in allografts. Cluster of differentiation 44 (CD44), as a cell adhesion receptor and is involved in cell migration, caused our interest in MMP-14/CD44 complex in allografts. Then we analyzed the effect of MMP-14/CD44 complex on pro-MMP-9 activation and vascular smooth muscle cell (VSMC) migration in rat VSMC TNF-α treated model. Then, we further found intervention of MMP-14/CD44 complex could inhibit VSMC migration. Our results elucidate the molecular mechanism of VSMC migration after cardiac transplantation and provide theoretical basis for seeking new specific drug targets for CAV prevention and treatment.
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Hua
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Kunpeng
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Rugao People's Hospital, Rugao, Jiangsu 226500, PR China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Sha
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Vasculocardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China. Electronic address: happysjh167@163.com.
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Vasculocardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China. Electronic address: ntwx0513@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
mesh_terms: D064591:Allografts; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016027:Heart Transplantation; D018960:Hyaluronan Receptors / Q000378:metabolism*; D064596:Isografts; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018960:Hyaluronan Receptors; D012697:Serine Endopeptidases; C463979:pro-MMP-9 activator; D053511:Matrix Metalloproteinase 14
keywords: CD44; Cardiac allograft vasculopathy; MMP-14; Migration; Vascular smooth muscle cell