title: Inhibition of fibroblast differentiation of muscle-derived stem cells in cell implantation treatment of stress urinary incontinence.
abstract: The aim of this study was to investigate the effects of transforming growth factor-β1 (TGF-β1) stimulation and the blocking of the TGF-β1/Smad3 signaling pathway by vector-mediated Smad3 shRNA on muscle-derived stem cells (MDSCs) in cell implantation treatment of stress urinary incontinence (SUI) of the rat. MDSCs were infected with the GC-shSmad3 lentivirus vector. Five days after infection, the cells were treated with TGF-β1. The expression levels of desmin (a marker of muscle differentiation) and vimentin (a marker of fibroblast differentiation) were tested by real-time PCR and Western blot. GC-shSmad3 lentivirus-infected MDSCs were injected into the bladder neck and proximal urethra of SUI rats. Urodynamic test was used to measure leak point pressure (LPP) at 2 weeks and 4 weeks after MDSC transplantation. Upregulated expression of vimentin and downregulated expression of desmin were found in MDSCs after culture with TGF-β1 in vitro. GC-shSmad3 lentivirus infection inhibited fibroblast differentiation of MDSCs but allowed muscle differentiation with desmin expression. In vivo experiments showed that GC-shSmad3 lentivirus infection could improve MDSC-mediated repairing of urethra sphincter function. In conclusion, blocking Smad3 expression inhibits the fibroblast differentiation of MDSCs induced by TGF-β1 in vitro and improves the repairing of urethral sphincter function by inhibiting the fibroblast differentiation of MDSCs in a rat model of SUI in vivo.
authors: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Yanzhou
authors: Y
authors: Wang
authors: Huicheng
authors: H
authors: Xu
authors: Xiaofang
authors: X
authors: Liu
authors: Lubin
authors: L
authors: Liu
authors: Zhiqing
authors: Z
authors: Liang
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation; D003893:Desmin / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D032446:Myoblasts / Q000378:metabolism* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism; D033581:Stem Cell Transplantation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014184:Transplantation, Homologous; D014521:Urethra / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism; D014549:Urinary Incontinence / Q000378:metabolism / Q000628:therapy*; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; D003893:Desmin; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014746:Vimentin