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Expression of TβR-2, Smad3 and Smad7 in the vaginal anterior wall of postpartum rats with stress urinary incontinence

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The objective of this study is to quantify and evaluate the expression of several important proteins in TGF-β1/Smad pathway in the anterior vaginal wall in postpartum rats with stress urinary incontinence (SUI).

Methods

Forty 8-week-old Sprague–Dawley (SD) female rats were randomized into three groups: blank group (n = 10), control group (n = 10) and SUI group (n = 20). Rats in blank group were non-pregnant, while rats in the control and SUI groups underwent normal parturition and normal parturition plus immediate postpartum vaginal balloon dilation, respectively. 1 week after dilation, a sneezing experiment and pad test were performed and the anterior vaginal wall was collected. The histological changes of the anterior vaginal wall were assessed by hematoxylin–eosin (HE) staining, and the expression of TβR-2, Smad3 and Smad7 in the anterior vaginal wall was detected by immunohistochemical staining and Western blotting.

Results

HE staining showed that collagen was more fragmented, sparse and disorganized in the SUI group compared with the control and blank groups. Compared with the blank group, the expression of TβR-2 and Smad7 protein was significantly increased in the vaginal anterior wall in the control and SUI groups (P < 0.05), while their levels in the SUI group were significantly higher than those in the control group (P < 0.05). Expression of Smad3 protein in the anterior vaginal wall of SUI rats was significantly decreased compared with the blank and control groups (P < 0.05).

Conclusion

Dysregulation of the TGF-β1/Smad signaling pathway may involve in the pathogenesis of SUI.

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Abbreviations

SUI:

Stress urinary incontinence

IHC:

Immunohistochemistry

ECM:

Extracellular matrix

TGF-β1:

Transforming growth factor-β1

TβR-2:

Transforming growth factor receptor II

References

  1. Chan SS, Cheung RY, Yiu KW, Lee LL, Chung TK (2013) Prevalence of urinary and fecal incontinence in Chinese women during and after their first pregnancy. Int Urogynecol J 24(9):1473–1479. doi:10.1007/s00192-012-2004-8

    Article  PubMed  Google Scholar 

  2. Findik RB, Unluer AN, Sahin E, Bozkurt OF, Karakaya J, Unsal A (2012) Urinary incontinence in women and its relation with pregnancy, mode of delivery, connective tissue disease and other factors. Adv Clin Exp Med 21(2):207–213

    PubMed  Google Scholar 

  3. Song Y, Hong X, Yu Y, Lin Y (2007) Changes of collagen type III and decorin in paraurethral connective tissue from women with stress urinary incontinence and prolapse. Int Urogynecol J Pelvic Floor Dysfunct 18(12):1459–1463. doi:10.1007/s00192-007-0356-2

    Article  PubMed  Google Scholar 

  4. Trabucco E, Soderberg M, Cobellis L, Torella M, Bystrom B, Ekman-Ordeberg G, Petraglia F, Colacurci N (2007) Role of proteoglycans in the organization of periurethral connective tissue in women with stress urinary incontinence. Maturitas 58(4):395–405. doi:10.1016/j.maturitas.2007.09.010

    Article  CAS  PubMed  Google Scholar 

  5. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J 16(17):5353–5362. doi:10.1093/emboj/16.17.5353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390(6659):465–471. doi:10.1038/37284

    Article  CAS  PubMed  Google Scholar 

  7. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P (1997) Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 389(6651):631–635. doi:10.1038/39369

    Article  CAS  PubMed  Google Scholar 

  8. Cutroneo KR, White SL, Phan SH, Ehrlich HP (2007) Therapies for bleomycin induced lung fibrosis through regulation of TGF-beta1 induced collagen gene expression. J Cell Physiol 211(3):585–589. doi:10.1002/jcp.20972

    Article  CAS  PubMed  Google Scholar 

  9. Jimenez SA, Varga J, Olsen A, Li L, Diaz A, Herhal J, Koch J (1994) Functional analysis of human alpha 1(I) procollagen gene promoter. Differential activity in collagen-producing and -nonproducing cells and response to transforming growth factor beta 1. J Biol Chem 269(17):12684–12691

    CAS  PubMed  Google Scholar 

  10. Chen SJ, Yuan W, Mori Y, Levenson A, Trojanowska M, Varga J (1999) Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3. J Invest Dermatol 112(1):49–57. doi:10.1046/j.1523-1747.1999.00477.x

    Article  CAS  PubMed  Google Scholar 

  11. Poncelet AC, Schnaper HW (2001) Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells. J Biol Chem 276(10):6983–6992. doi:10.1074/jbc.M006442200

    Article  CAS  PubMed  Google Scholar 

  12. Li GY, Cui WS, Zhou F, Gao ZZ, Xin H, Liu T, Li WR, Gong YQ, Bai GY, Guo YL, Xin ZC (2012) Pathology of urethral fibromuscular system related to parturition-induced stress urinary incontinence and TGF-beta1/Smad pathway. Mol Cell Biochem 364(1–2):329–335. doi:10.1007/s11010-012-1234-x

    Article  CAS  PubMed  Google Scholar 

  13. Qiang F, Guo-long L (2011) Comparative study of three rat models of stress urinary incontinence. Bosn J Basic Med Sci 11(2):87–90

    PubMed  Google Scholar 

  14. Heidkamp MC, Leong FC, Brubaker L, Russell B (1998) Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats. Int Urogynecol J Pelvic Floor Dysfunct 9(2):88–93

    Article  CAS  PubMed  Google Scholar 

  15. Pauwels E, De Wachter S, Wyndaele JJ (2009) Evaluation of different techniques to create chronic urinary incontinence in the rat. BJU Int 103(6):782–785. doi:10.1111/j.1464-410X.2008.08158.x (discussion 785–786)

    Article  PubMed  Google Scholar 

  16. Liebergall-Wischnitzer M, Paltiel O, Hochner-Celnikier D, Lavy Y, Shveiky D, Manor O (2010) Concordance between one-hour pad test and subjective assessment of stress incontinence. Urology 76(6):1364–1368. doi:10.1016/j.urology.2010.05.048

    Article  CAS  PubMed  Google Scholar 

  17. Hochstim CJ, Choi JY, Lowe D, Masood R, Rice DH (2010) Biofilm detection with hematoxylin–eosin staining. Arch Otolaryngol Head Neck Surg 136(5):453–456. doi:10.1001/archoto.2010.62

    Article  PubMed  Google Scholar 

  18. Goepel C, Thomssen C (2006) Changes in the extracellular matrix in periurethral tissue of women with stress urinary incontinence. Acta Histochem 108(6):441–445. doi:10.1016/j.acthis.2006.07.001

    Article  PubMed  Google Scholar 

  19. Chen B, Yeh J (2011) Alterations in connective tissue metabolism in stress incontinence and prolapse. J Urol 186(5):1768–1772. doi:10.1016/j.juro.2011.06.054

    Article  CAS  PubMed  Google Scholar 

  20. Goepel C, Hefler L, Methfessel HD, Koelbl H (2003) Periurethral connective tissue status of postmenopausal women with genital prolapse with and without stress incontinence. Acta Obstet Gynecol Scand 82(7):659–664

    Article  PubMed  Google Scholar 

  21. Edwall L, Carlstrom K, Jonasson AF (2005) Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence. Neurourol Urodyn 24(4):319–324. doi:10.1002/nau.20142

    Article  CAS  PubMed  Google Scholar 

  22. Wen Y, Polan ML, Chen B (2006) Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence? Hum Reprod 21(5):1266–1273. doi:10.1093/humrep/dei485

    Article  CAS  PubMed  Google Scholar 

  23. Wen Y, Zhao YY, Polan ML, Chen B (2008) Effect of relaxin on TGF-beta1 expression in cultured vaginal fibroblasts from women with stress urinary incontinence. Reprod Sci 15(3):312–320. doi:10.1177/1933719108315299

    Article  CAS  PubMed  Google Scholar 

  24. Zandvoort A, Postma DS, Jonker MR, Noordhoek JA, Vos JT, van der Geld YM, Timens W (2006) Altered expression of the Smad signalling pathway: implications for COPD pathogenesis. Eur Respir J 28(3):533–541. doi:10.1183/09031936.06.00078405

    Article  CAS  PubMed  Google Scholar 

  25. Medina C, Santos-Martinez MJ, Santana A, Paz-Cabrera MC, Johnston MJ, Mourelle M, Salas A, Guarner F (2011) Transforming growth factor-beta type 1 receptor (ALK5) and Smad proteins mediate TIMP-1 and collagen synthesis in experimental intestinal fibrosis. J Pathol 224(4):461–472. doi:10.1002/path.2870

    Article  CAS  PubMed  Google Scholar 

  26. Moro T, Shimoyama Y, Kushida M, Hong YY, Nakao S, Higashiyama R, Sugioka Y, Inoue H, Okazaki I, Inagaki Y (2008) Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis. Life Sci 83(15–16):531–539. doi:10.1016/j.lfs.2008.07.023

    Article  CAS  PubMed  Google Scholar 

  27. Chiang TA, Yang YL, Yang YY, Hu MH, Wu PF, Liu SF, Huang RM, Liao TN, Hung CY, Hung TJ, Lee TC (2010) Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor-beta receptors. J Cell Biochem 109(4):663–671. doi:10.1002/jcb.22444

    CAS  PubMed  Google Scholar 

  28. Phanish MK, Wahab NA, Colville-Nash P, Hendry BM, Dockrell ME (2006) The differential role of Smad2 and Smad3 in the regulation of pro-fibrotic TGFbeta1 responses in human proximal-tubule epithelial cells. Biochem J 393(Pt 2):601–607. doi:10.1042/bj20051106

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Yang F, Chung AC, Huang XR, Lan HY (2009) Angiotensin II induces connective tissue growth factor and collagen I expression via transforming growth factor-beta-dependent and -independent Smad pathways: the role of Smad3. Hypertension 54(4):877–884. doi:10.1161/hypertensionaha.109.136531

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a Grant from the Science Technology and Information Bureau of Guangzhou (Grant No. 201300000137) and a fund for Excellent Talents in the Third Affiliated Hospital of Guangzhou Medical University.

Conflict of interest

We declare that we have no conflict of interest. We state that we have had full control of all primary data and we agree to allow the Journal to review our data if requested.

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Correspondence to Juan Liu.

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Wang, H., Liu, J., Zeng, J. et al. Expression of TβR-2, Smad3 and Smad7 in the vaginal anterior wall of postpartum rats with stress urinary incontinence. Arch Gynecol Obstet 291, 869–876 (2015). https://doi.org/10.1007/s00404-014-3495-y

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  • DOI: https://doi.org/10.1007/s00404-014-3495-y

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