title: TGF-β/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial cystitis after urinary bladder transplantation.
abstract: OBJECTIVE
  This study aimed to explore the role of the transforming growth factor-β/mitogen activated protein kinase (TGF-β/MAPK) signaling pathway in the effects of bone marrow mesenchymal stem cells (BMSCs) on urinary control and interstitial cystitis in a rat model of urinary bladder transplantation.
  
  
  METHODS
  A urinary bladder transplantation model was established using Sprague-Dawley rats. Rats were assigned to normal (blank control), negative control (phosphate-buffered saline injection), BMSCs (BMSC injection), sp600125 (MAPK inhibitor injection), or protamine sulfate (protamine sulfate injection) groups. Immunohistochemistry, urodynamic testing, hematoxylin-eosin staining, Western blotting, enzyme-linked immunosorbent assay, and MTT assay were used to assess BMSC growth, the kinetics of bladder urinary excretion, pathological changes in bladder tissue, bladder tissue ultrastructure, the expression of TGF-β/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and the effects of antiproliferative factor on cell proliferation.
  
  
  RESULTS
  Compared with normal, negative control, BMSCs, and sp600125 groups, rats in the PS group exhibited decreased discharge volume, maximal micturition volume, contraction interval, and bladder capacity but increased residual urine volume, bladder pressure, bladder peak pressure, expression of TGF-β/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and growth inhibition rate. Levels of inflammatory cytokines and the growth inhibition rate were positively correlated with the expression of TGF-β/MAPK signaling pathway-related proteins.
  
  
  CONCLUSIONS
  Our findings demonstrate that the TGF-β/MAPK signaling pathway mediates the beneficial effects of BMSCs on urinary control and interstitial cystitis.
authors.affiliation: Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical UniversityChongqing 400037, P. R. China; Department of Urology, The Second Affiliated Hospital, The Third Military Medical UniversityChongqing 400037, P. R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Urology, The Second Affiliated Hospital, The Third Military Medical University Chongqing 400037, P. R. China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical University Chongqing 400037, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Urology, The Second Affiliated Hospital, The Third Military Medical University Chongqing 400037, P. R. China.
authors.forename: Chi-Bing
authors.initials: CB
authors.lastname: Huang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ling
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
keywords: TGF-β/MAPK signaling pathway; bladder transplantation; bone marrow mesenchymal stem cells; interstitial cystitis; urinary control