Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 4/2015

01-04-2015 | General Gynecology

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

Authors: Hailan Wang, Juan Liu, Jie Zeng, Chunyan Zeng, Yan Zhou

Published in: Archives of Gynecology and Obstetrics | Issue 4/2015

Login to get access

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.
Literature
2.
go back to reference 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):207–213PubMed 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):207–213PubMed
3.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
4.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
7.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
8.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
9.
go back to reference 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):12684–12691PubMed 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):12684–12691PubMed
11.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
12.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
13.
go back to reference Qiang F, Guo-long L (2011) Comparative study of three rat models of stress urinary incontinence. Bosn J Basic Med Sci 11(2):87–90PubMed Qiang F, Guo-long L (2011) Comparative study of three rat models of stress urinary incontinence. Bosn J Basic Med Sci 11(2):87–90PubMed
14.
go back to reference 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):88–93CrossRefPubMed 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):88–93CrossRefPubMed
20.
go back to reference 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):659–664CrossRefPubMed 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):659–664CrossRefPubMed
21.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
22.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
25.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
26.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
27.
go back to reference 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 PubMed 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 PubMed
28.
go back to reference 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 PubMedCentralPubMed 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 PubMedCentralPubMed
29.
Metadata
Title
Expression of TβR-2, Smad3 and Smad7 in the vaginal anterior wall of postpartum rats with stress urinary incontinence
Authors
Hailan Wang
Juan Liu
Jie Zeng
Chunyan Zeng
Yan Zhou
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 4/2015
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-014-3495-y

Other articles of this Issue 4/2015

Archives of Gynecology and Obstetrics 4/2015 Go to the issue