Full Text:   <988>

Summary:  <331>

CLC number: Q95

On-line Access: 2015-10-03

Received: 2015-02-26

Revision Accepted: 2015-05-07

Crosschecked: 2015-09-13

Cited: 3

Clicked: 1582

Citations:  Bibtex RefMan EndNote GB/T7714


Wen Zong


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.10 P.857-864


Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

Author(s):  Wen Zong, Yan Jiang, Jing Zhao, Jian Zhang, Jian-gang Gao

Affiliation(s):  Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China

Corresponding email(s):   zhaojing@sdu.edu.cn, zhj8226@sdu.edu.cn

Key Words:  Estradiol, Lysyl oxidase family genes, TGF-β, signal pathway

Wen Zong, Yan Jiang, Jing Zhao, Jian Zhang, Jian-gang Gao. Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells[J]. Journal of Zhejiang University Science B, 2015, 16(10): 857-864.

@article{title="Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells",
author="Wen Zong, Yan Jiang, Jing Zhao, Jian Zhang, Jian-gang Gao",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells
%A Wen Zong
%A Yan Jiang
%A Jing Zhao
%A Jian Zhang
%A Jian-gang Gao
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 10
%P 857-864
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500048

T1 - Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells
A1 - Wen Zong
A1 - Yan Jiang
A1 - Jing Zhao
A1 - Jian Zhang
A1 - Jian-gang Gao
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 10
SP - 857
EP - 864
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500048

The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells. Mice and Ishikawa cells treated with estradiol (E2) showed increased expression of LOX family genes and transforming growth factor β1 (TGF-β;1). Ishikawa cells treated with TGF-β;1 also showed increased expression of LOX family genes. The Ishikawa cells were then treated with either E2 plus the TGF-β; receptor (TGFBR) inhibitor SB431542 or E2 alone. The expression of LOX family genes induced by E2 was reduced in the Ishikawa cells treated with TGFBR inhibitor. Our results showed that E2 increased the expression of the LOX family genes, and suggest that this induction may be mediated by the TGF-β; signal pathway. E2 may play a role in regulating the expression of LOX family genes.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Alarab, M., Bortolini, M.A., Drutz, H., et al., 2010. LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse. Int. Urogynecol. J., 21(11):1397-1404.

[2]Bai, S.W., Chung, D.J., Yoon, J.M., et al., 2005. Roles of estrogen receptor, progesterone receptor, p53 and p21 in pathogenesis of pelvic organ prolapse. Int. Urogynecol. J., 16(6):492-496.

[3]Balgobin, S., Montoya, T.I., Shi, H., et al., 2013. Estrogen alters remodeling of the vaginal wall after surgical injury in guinea pigs. Biol. Reprod., 89(6):138.

[4]Derynck, R., Gelbart, W.M., Harland, R.M., et al., 1996. Nomenclature: vertebrate mediators of TGFβ family signals. Cell, 87(2):173.

[5]Drewes, P.G., Marinis, S.I., Acevedo, J., et al., 2005. Paper 17: regulation of lysyl oxidase in the vaginal wall: role of estrogen, progesterone, and pregnancy. J. Pelvic Med. Surg., 11:S8-S9.

[6]Drewes, P.G., Yanagisawa, H., Starcher, B., et al., 2007. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am. J. Pathol., 170(2):578-589.

[7]Gantus, M.A.V., Alves, L.M., Stipursky, J., et al., 2011. Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells. Mol. Cell. Endocrinol., 337(1-2):71-79.

[8]Goepel, C., 2008. Differential elastin and tenascin immunolabeling in the uterosacral ligaments in postmenopausal women with and without pelvic organ prolapse. Acta Histochem., 110(3):204-209.

[9]Guo, R.X., Wei, L.H., Tu, Z., et al., 2006. 17β-Estradiol activates PI3K/Akt signaling pathway by estrogen receptor (ER)-dependent and ER-independent mechanisms in endometrial cancer cells. J. Steroid Biochem. Mol. Biol., 99(1):9-18.

[10]Guo, X., Zhou, G., Guo, M., et al., 2014. Adiponectin retards the progression of diabetic nephropathy in db/db mice by counteracting angiotensin II. Physiol. Rep., 2(2):e00230.

[11]Handa, V.L., Cundiff, G., Chang, H.H., et al., 2008. Female sexual function and pelvic floor disorders. Obstet. Gynecol., 111(5):1045-1052.

[12]Herpin, A., Lelong, C., Favrel, P., et al., 2004. Transforming growth factor-β-related proteins: an ancestral and widespread superfamily of cytokines in metazoans. Develop. Comp. Immunol., 28(5):461-485.

[13]Hornstra, I.K., Birge, S., Starcher, B., et al., 2003. Lysyl oxidase is required for vascular and diaphragmatic development in mice. J. Biol. Chem., 278(16):14387-14393.

[14]Hunskaar, S., Burgio, K., Clark, A., et al., 2005. Epidemiology of urinary (UI) and faecal (FI) incontinence and pelvic organ prolapse (POP). WHO-ICS International Consultation on Incontinence, 3rd Ed. Health Publications Ltd., Paris, p.255-312.

[15]Jiang, Y., Zhao, J., Qi, H.J., et al., 2013. Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 14(4):318-324.

[16]Jiang, Y., Zong, W., Luan, H., et al., 2014. Decreased expression of elastin and lysyl oxidase family genes in urogenital tissues of aging mice. J. Obstet. Gynaecol. Res., 40(8):1998-2004.

[17]Karam, J.A., Vazquez, D.V., Lin, V.K., et al., 2007. Elastin expression and elastic fibre width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int., 100(2):346-350.

[18]Kenyon, N.J., Ward, R.W., McGrew, G., et al., 2003. TGF-β1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax, 58(9):772-777.

[19]Klutke, J., Ji, Q., Campeau, J., et al., 2008. Decreased endopelvic fascia elastin content in uterine prolapse. Acta Obstet. Gynecol. Scand., 87(1):111-115.

[20]Kobak, W., Lu, J., Hardart, A., et al., 2005. Expression of lysyl oxidase and transforming growth factor β2 in women with severe pelvic organ prolapse. J. Reprod. Med., 50(11):827-831.

[21]Lang, J.H., Zhu, L., Sun, Z.J., et al., 2003. Estrogen levels and estrogen receptors in patients with stress urinary incontinence and pelvic organ prolapse. Int. J. Gynaecol. Obstet., 80(1):35-39.

[22]Lindberg, M.K., Moverare, S., Eriksson, A.L., et al., 2002. Identification of estrogen-regulated genes of potential importance for the regulation of trabecular bone mineral density. J. Bone Miner. Res., 17(12):2183-2195.

[23]Liu, X., Zhao, Y., Gao, J., et al., 2004. Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat. Genet., 36(2):178-182.

[24]Liu, X., Zhao, Y., Pawlyk, B., et al., 2006. Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am. J. Pathol., 168(2):519-528.

[25]Maurya, V.K., Jha, R.K., Kumar, V., et al., 2013. Transforming growth factor-beta 1 (TGF-B1) liberation from its latent complex during embryo implantation and its regulation by estradiol in mouse. Biol. Reprod., 89(4):84.

[26]Olsen, A.L., Smith, V.J., Bergstrom, J.O., et al., 1997. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet. Gynecol., 89(4):501-506.

[27]Sethi, A., Mao, W., Wordinger, R.J., et al., 2011. Transforming growth factor-β induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci., 52(8):5240-5250.

[28]Shimizu, Y., 2010. Estrogen: estrone (E1), estradiol (E2), estriol (E3) and estetrol (E4). Nihon Rinsho, 68(7):448-461 (in Japanese).

[29]Soares, R., Guo, S., Gartner, F., et al., 2003. 17β-Estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGFβ and EGFR crosstalk. Angiogenesis, 6(4):271-281.

[30]Son, E.D., Lee, J.Y., Lee, S., et al., 2005. Topical application of 17β-estradiol increases extracellular matrix protein synthesis by stimulating TGF-β signaling in aged human skin in vivo. J. Invest. Dermatol., 124(6):1149-1161.

[31]Takahashi, T., Eitzman, B., Bossert, N.L., et al., 1994. Transforming growth factors β1, β2, and β3 messenger RNA and protein expression in mouse uterus and vagina during estrogen-induced growth: a comparison to other estrogen-regulated genes. Cell Growth Differ., 5(9):919-935.

[32]Tsubaki, M., Yamazoe, Y., Yanae, M., et al., 2011. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma. Cytokine, 54(1):100-107.

[33]Voloshenyuk, T.G., Larkin, K., Fournett, A., et al., 2012. Estrogen receptor dependence of lysyl oxidase expression and activity in cardiac fibroblasts. FASEB J., 26:1059.16.

[34]Wu, D., Peng, F., Zhang, B., et al., 2009. PKC-β1 mediates glucose-induced Akt activation and TGF-β1 upregulation in mesangial cells. J. Am. Soc. Nephrol., 20(3):554-566.

[35]Xie, J., Wang, C., Huang, D.Y., et al., 2013. TGF-β1 induces the different expressions of lysyl oxidases and matrix metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after mechanical injury. J. Biomech., 46(5):890-898.

[36]Yasui, T., Saijo, A., Uemura, H., et al., 2009. Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy. Eur. J. Endocrinol., 161(2):267-273.

[37]Yu, L., Wang, C.Y., Shi, J., et al., 2011. Estrogens promote invasion of prostate cancer cells in a paracrine manner through up-regulation of matrix metalloproteinase 2 in prostatic stromal cells. Endocrinology, 152(3):773-781.

[38]Zhang, S.Q., Zhang, L.L., Yu, H., 2008. Expression of elastin, lysyl oxidase and elafin in the cardinal ligament of women with pelvic organ prolapse. Chin. J. Obstet. Gynecol., 43(9):675-679 (in Chinese).

[39]Zhao, B.H., Zhou, J.H., 2012. Decreased expression of elastin, fibulin-5 and lysyl oxidase-like 1 in the uterosacral ligaments of postmenopausal women with pelvic organ prolapse. J. Obstet. Gynaecol. Res., 38(6):925-931.

[40]Zhou, Y., Ling, O., Bo, L., 2013. 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(1):23-28.

[41]Zong, W., Stein, S.E., Starcher, B., et al., 2010. Alteration of vaginal elastin metabolism in women with pelvic organ prolapse. Obstet. Gynecol., 115(5):953-961.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE