Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse

Li,Bing‑Shu; Guo,Wen‑Jun; Hong,Li; Liu,Yao‑Dan; Liu,Cheng; Hong,Sha‑Sha; Wu,De‑Bin; Min,Jie

doi:10.3892/mmr.2016.5264

Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse

Authors:
- Bing‑Shu Li
- Wen‑Jun Guo
- Li Hong
- Yao‑Dan Liu
- Cheng Liu
- Sha‑Sha Hong
- De‑Bin Wu
- Jie Min
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Affiliations: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: May 13, 2016 https://doi.org/10.3892/mmr.2016.5264
Pages: 243-253
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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