title: Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse.
abstract: Mechanical loading on pelvic supports contributes to pelvic organ prolapse (POP). However, the underlying mechanisms remain to be elucidated. Our previous study identified that mechanical strain induced oxidative stress (OS) and promoted apoptosis and senescence in pelvic support fibroblasts. The aim of the present study is to investigate the molecular signaling pathway linking mechanical force with POP. Using a four‑point bending device, human uterosacral ligament fibroblasts (hUSLF) were exposed to mechanical tensile strain at a frequency of 0.3 Hz and intensity of 5333 µε, in the presence or absence of LY294002. The applied mechanical strain on hUSLF resulted in apoptosis and senescence, and decreased expression of procollagen type I α1. Mechanical strain activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling and resulted in downregulated expression of glutathione peroxidase 1 and Mn‑superoxide dismutase, and accumulation of intracellular reactive oxygen species. These effects were blocked by administration of LY294002. Furthermore, it was demonstrated that PI3K/Akt was activated in the uterosacral ligaments of POP patients, and that OS was increased and collagen type I production reduced. The results from the present study suggest that mechanical strain promotes apoptosis and senescence, and reduces collagen type I production via activation of PI3K/Akt-mediated OS signaling pathway in hUSLF. This process may be involved in the pathogenesis of POP as it results in relaxation and dysfunction of pelvic supports.
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Bing-Shu
authors.initials: BS
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yao-Dan
authors.initials: YD
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Hong
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: De-Bin
authors.initials: DB
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Min
mesh_terms: D000368:Aged; D017209:Apoptosis; D016922:Cellular Senescence; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008022:Ligaments / Q000166:cytology; D055595:Mechanical Phenomena; D008875:Middle Aged; D018384:Oxidative Stress; D056887:Pelvic Organ Prolapse / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt