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Article Open Access

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
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 243-253
    |
    Published online on: May 13, 2016
       https://doi.org/10.3892/mmr.2016.5264
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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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1 

Jelovsek JE, Maher C and Barber MD: Pelvic organ prolapse. Lancet. 369:1027–1038. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Virtanen HS and Mäkinen JI: Retrospective analysis of 711 patients operated on for pelvic relaxation in 1983–1989. Int J Gynaecol Obstet. 42:109–115. 1993. View Article : Google Scholar : PubMed/NCBI

3 

Gyhagen M, Bullarbo M, Nielsen TF and Milsom I: Prevalence and risk factors for pelvic organ prolapse 20 years after childbirth: A national cohort study in singleton primiparae after vaginal or caesarean delivery. BJOG. 120:152–160. 2013. View Article : Google Scholar

4 

Chow D and Rodríguez LV: Epidemiology and prevalence of pelvic organ prolapse. Curr Opin Urol. 23:293–298. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Miedel A, Tegerstedt G, Mæhle-Schmidt M, Nyrén O and Hammarström M: Nonobstetric risk factors for symptomatic pelvic organ prolapse. Obstet Gynecol. 113:1089–1097. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Paterno J, Vial IN, Wong VW, Rustad KC, Sorkin M, Shi Y, Bhatt KA, Thangarajah H, Glotzbach JP and Gurtner GC: Akt-mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation. Wound Repair Regen. 19:49–58. 2011. View Article : Google Scholar

7 

Zhou Y, Ling O and Bo L: Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction. J Biomed Res. 27:23–28. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Budatha M, Silva S, Montoya TI, Suzuki A, Shah-Simpson S, Wieslander CK, Yanagisawa M, Word RA and Yanagisawa H: Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse. PloS One. 8:e563762013. View Article : Google Scholar : PubMed/NCBI

9 

Li BS, Hong L, Min J, Wu DB, Hu M and Guo WJ: The expression of glutathione peroxidase-1 and the anabolism of collagen regulation pathway transforming growth factor-beta1-connective tissue growth factor in women with uterine prolapse and the clinic significance. Clin Exp Obstet Gynecol. 40:586–590. 2013.PubMed/NCBI

10 

Konstantonis D, Papadopoulou A, Makou M, Eliades T, Basdra E and Kletsas D: The role of cellular senescence on the cyclic stretching-mediated activation of MAPK and ALP expression and activity in human periodontal ligament fibroblasts. Exp Gerontol. 57:175–180. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Yue Y, Lypowy J, Hedhli N and Abdellatif M: Ras GTPase-activating protein binds to Akt and is required for its activation. J Biol Chem. 279:12883–12889. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Nho RS, Xia H, Kahm J, Kleidon J, Diebold D and Henke CA: Role of integrin-linked kinase in regulating phosphorylation of Akt and fibroblast survival in type I collagen matrices through a beta1 integrin viability signaling pathway. J Biol Chem. 280:26630–26639. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Thompson WR, Rubin CT and Rubin J: Mechanical regulation of signaling pathways in bone. Gene. 503:179–193. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Xue Z, Zhang W, Desai LP, Gao H, Gunst SJ and Tepper RS: Increased mechanical strain imposed on murine lungs during ventilation in vivo depresses airway responsiveness and activation of protein kinase Akt. J Appl Physiol (1985). 114:1506–1510. 2013. View Article : Google Scholar

15 

Boccafoschi F, Bosetti M, Sandra PM, Leigheb M and Cannas M: Effects of mechanical stress on cell adhesion: A possible mechanism for morphological changes. Cell Adh Migr. 4:19–25. 2010. View Article : Google Scholar :

16 

Premaraj S, Souza I and Premaraj T: Mechanical loading activates β-catenin signaling in periodontal ligament cells. Angle Orthod. 81:592–599. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Hong SS, Ding WJ, Wu DB, Min J, Hong L, et al: Effects of oxidative damage in human parametrial ligament fibroblasts induced by mechanical stress. Chin J Clinicians (Electronic Edition). 7:10775–10779. 2013.

18 

Usta A, Guzin K, Kanter M, Ozgül M and Usta CS: Expression of matrix metalloproteinase-1 in round ligament and uterosacral ligament tissue from women with pelvic organ prolapse. J Mol Histol. 45:275–281. 2014. View Article : Google Scholar

19 

Kim EJ, Chung N, Park SH, Lee KH, Kim SW, Kim JY, Bai SW and Jeon MJ: Involvement of oxidative stress and mitochondrial apoptosis in the pathogenesis of pelvic organ prolapse. J Urol. 189:588–594. 2013. View Article : Google Scholar

20 

Zhang X, Tang N, Hadden TJ and Rishi AK: Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 1813:1978–1986. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Fu Z and Tindall DJ: FOXOs, cancer and regulation of apoptosis. Oncogene. 27:2312–2319. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Downing JR: A new FOXO pathway required for leukemogenesis. Cell. 146:669–670. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Tzivion G and Hay N: PI3K-AKT-FoxO axis in cancer and aging. Biochim Biophys Acta. 1813:19252011. View Article : Google Scholar : PubMed/NCBI

24 

Hong S, Li H, Wu D, Li B, Liu C, Guo W, Min J, Hu M, Zhao Y and Yang Q: Oxidative damage to human parametrial ligament fibroblasts induced by mechanical stress. Mol Med Rep. 12:5342–5348. 2015.PubMed/NCBI

25 

Ding WJ, Hong SS, Min J, Fang G, Zhang X, Hu M, Yang Q and Hong L: Preliminary study on primary culture of human parametrial ligament fibroblasts. Medical Journal of Wuhan University. 35:16–19. 2014.

26 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

27 

Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 92:9363–9367. 1995. View Article : Google Scholar : PubMed/NCBI

28 

Franklin JL: Redox regulation of the intrinsic pathway in neuronal apoptosis. Antioxid Redox Signal. 14:1437–1448. 2011. View Article : Google Scholar :

29 

Labunskyy VM and Gladyshev VN: Role of reactive oxygen species-mediated signaling in aging. Antioxid Redox Signal. 19:1362–1372. 2013. View Article : Google Scholar :

30 

Finkel T and Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature. 408:239–247. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Mori R, Tanaka K, de Kerckhove M, Okamoto M, Kashiyama K, Tanaka K, Kim S, Kawata T, Komatsu T, Park S, et al: Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring. Am J Pathol. 184:2465–2479. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Danciu TE, Gagari E, Adam RM, Damoulis PD and Freeman MR: Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts. J Dent Res. 83:596–601. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Chae HD and Broxmeyer HE: SIRT1 deficiency downregulates PTEN/JNK/FOXO1 pathway to block reactive oxygen species-induced apoptosis in mouse embryonic stem cells. Stem Cells Dev. 20:1277–1285. 2011. View Article : Google Scholar :

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Copy and paste a formatted citation
Spandidos Publications style
Li BS, Guo WJ, Hong L, Liu YD, Liu C, Hong SS, Wu DB and Min J: Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse. Mol Med Rep 14: 243-253, 2016.
APA
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S. ... Min, J. (2016). Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse. Molecular Medicine Reports, 14, 243-253. https://doi.org/10.3892/mmr.2016.5264
MLA
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S., Wu, D., Min, J."Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse". Molecular Medicine Reports 14.1 (2016): 243-253.
Chicago
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S., Wu, D., Min, J."Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse". Molecular Medicine Reports 14, no. 1 (2016): 243-253. https://doi.org/10.3892/mmr.2016.5264
Copy and paste a formatted citation
x
Spandidos Publications style
Li BS, Guo WJ, Hong L, Liu YD, Liu C, Hong SS, Wu DB and Min J: Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse. Mol Med Rep 14: 243-253, 2016.
APA
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S. ... Min, J. (2016). Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse. Molecular Medicine Reports, 14, 243-253. https://doi.org/10.3892/mmr.2016.5264
MLA
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S., Wu, D., Min, J."Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse". Molecular Medicine Reports 14.1 (2016): 243-253.
Chicago
Li, B., Guo, W., Hong, L., Liu, Y., Liu, C., Hong, S., Wu, D., Min, J."Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse". Molecular Medicine Reports 14, no. 1 (2016): 243-253. https://doi.org/10.3892/mmr.2016.5264
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