title: Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.
abstract: OBJECTIVE
  To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs).
  
  
  METHODS
  HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection.
  
  
  RESULTS
  The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK.
  
  
  CONCLUSIONS
  Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Shulian
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Chuandu
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Deyi
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Tongxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China. wangkj@scu.edu.cn.
authors.forename: Kunjie
authors.initials: K
authors.lastname: Wang
mesh_terms: D001696:Biomechanical Phenomena; D015153:Blotting, Western; D024042:Collagen Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D039441:Integrin alpha4 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D039564:Integrin alphaV / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D001743:Urinary Bladder / Q000166:cytology
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005419:Flavonoids; D039564:Integrin alphaV; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D039441:Integrin alpha4; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Bladder smooth muscle cells; Extracellular matrix; Extracellular regulated protein kinases 1/2; Focal adhesion kinase; Integrin; Simulated physiological stretch