title: Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs.
abstract: Mechanical stimulation is an essential factor for organisms to develop normally. In bladder development matrix metalloproteinases (MMPs) play an important role through structure remodeling and regulating the cell proliferation. In this study, we investigated the simulated physiological stretch induced proliferation of HBSMCs; MMPs/TIMPs expression in stretch and non-stretch groups. HBSMCs were exposed to cyclic stretch with defined parameters (5%, 10% and 15% elongation). The expression of MMPs and TIMPs in each parameter and non-stretch groups was examined at the transcriptional and translational levels respectively. 5-Ethynyl-2'-deoxyuridine (EdU) assay was used to assess cell proliferation. In the presence of the broad spectrum MMPs inhibitor (Batimastat), cells proliferation, MMPs and tissue inhibitors of metalloproteinases (TIMPs) expression were assessed again. Compared with non-stretch group, HBSMCs in stretch groups showed higher proliferation. The expression of MMP-1, 2, 3, 7 was up-regulated in stretch groups, and it remained at the same high level in 10% and 15% stretch groups. TIMP-1, 2 expression only increased under 15% stretch. Stretch resulted in elevated cell proliferation was abolished by Batimastat. In conclusion, the proliferation of HBSMCs induced by stretch was resulted from the stretch-induced MMPs expression and release.
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Bu
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Chuandu
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Cao
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041,China. Electronic address: wzwzlscu@qq.com.
authors.forename: Kunjie
authors.initials: K
authors.lastname: Wang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder
chemical_list: D011480:Protease Inhibitors; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D013876:Thiophenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D010649:Phenylalanine; C080985:batimastat; D017364:Collagenases
keywords: Cell proliferation; Matrix metalloproteinases; Smooth muscle cell; Stretch; Urinary bladder