Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses Corrigendum in /10.3892/mmr.2020.11721

Zhang,Liping; Dai,Fangfang; Chen,Gantao; Wang,Yanqing; Liu,Shiyi; Zhang,Li; Xian,Shu; Yuan,Mengqin; Yang,Dongyong; Zheng,Yajing; Deng,Zhimin; Cheng,Yanxiang; Yang,Xiaofeng

doi:10.3892/mmr.2020.11564

Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses

Corrigendum in: /10.3892/mmr.2020.11721

Authors:
- Liping Zhang
- Fangfang Dai
- Gantao Chen
- Yanqing Wang
- Shiyi Liu
- Li Zhang
- Shu Xian
- Mengqin Yuan
- Dongyong Yang
- Yajing Zheng
- Zhimin Deng
- Yanxiang Cheng
- Xiaofeng Yang
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Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Gastroenterology, Third People's Hospital of Xiantao in Hubei Province, Xiantao, Hubei 433000, P.R. China
Published online on: October 6, 2020 https://doi.org/10.3892/mmr.2020.11564
Pages: 4611-4618
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pelvic organ prolapses (POP) notably reduces the quality of life in elderly populations due to bladder and bowel dysfunction, incontinence, and coital problems. Extracellular matrix (ECM) disorder is a pivotal event in the progression of POP, but to date, its specific underlying mechanism remains unclear. The ligaments of patients with POP and healthy controls were collected to compare the expression of Homeobox11 (HOXA11) and transforming growth factor β (TGF‑β1) via immunohistochemical analysis. HOXA11 and TGF‑β1 were overexpressed or knocked down in fibroblast cells to explore their effects on the expression of collagen and matrix metalloproteinases (MMPs). HOXA11 and TGF‑β1 were greatly reduced in the ligaments of patients with POP. The overexpression and downregulation of HOXA11 and TGF‑β1 can mediate ECM disorder via regulating expression of collagen (Col) and MMPs. In addition, HOXA11 and TGF‑β1 exerted synergistic effect on the expression of Col and MMPs. The present study identified that HOXA11 and TGF‑β1 serve critical roles in mediating ECM disorders, which may be of clinical significance for the diagnosis and treatment of patients with POP.

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1	Vergeldt TF, Weemhoff M, IntHout J and Kluivers KB: Risk factors for pelvic organ prolapse and its recurrence: A systematic review. Int Urogynecol J. 26:1559–1573. 2015. View Article : Google Scholar : PubMed/NCBI
2	Altman D, Zetterstrom J, Schultz I, Nordenstam J, Hjern F, Lopez A and Mellgren A: Pelvic organ prolapse and urinary incontinence in women with surgically managed rectal prolapse: A population-based case-control study. Dis Colon Rectum. 49:28–35. 2006. View Article : Google Scholar : PubMed/NCBI
3	Clark AL, Gregory T, Smith VJ and Edwards R: Epidemiologic evaluation of reoperation for surgically treated pelvic organ prolapse and urinary incontinence. Am J Obstet Gynecol. 189:1261–1267. 2003. View Article : Google Scholar : PubMed/NCBI
4	Olsen AL, Smith VJ, Bergstrom JO, Colling JC and Clark AL: Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol. 89:501–506. 1997. View Article : Google Scholar : PubMed/NCBI
5	Delancey JO, Kane Low L, Miller JM, Patel DA and Tumbarello JA: Graphic integration of causal factors of pelvic floor disorders: An integrated life span model. Am J Obstet Gynecol. 199:610.e1–e5. 2008. View Article : Google Scholar
6	Zhao X, Ma C, Li R, Xue J, Liu L and Liu P: Hypoxia induces apoptosis through HIF-1α signaling pathway in human uterosacral ligaments of pelvic organ prolapse. Biomed Res Int. 2017:83160942017. View Article : Google Scholar : PubMed/NCBI
7	Sun MJ, Cheng YS, Liu CS and Sun R: Changes in the PGC-1α and mtDNA copy number may play a role in the development of pelvic organ prolapse in pre-menopausal patients. Taiwan J Obstet Gynecol. 58:526–530. 2019. View Article : Google Scholar : PubMed/NCBI
8	Zhang L, Zheng P, Duan A, Hao Y, Lu C and Lu D: [Corrigendum] Genomewide DNA methylation analysis of uterosacral ligaments in women with pelvic organ prolapse. Mol Med Rep. 19:24582019.PubMed/NCBI
9	Tyagi T, Alarab M, Leong Y, Lye S and Shynlova O: Local oestrogen therapy modulates extracellular matrix and immune response in the vaginal tissue of post-menopausal women with severe pelvic organ prolapse. J Cell Mol Med. 23:2907–2919. 2019. View Article : Google Scholar : PubMed/NCBI
10	Alarab M, Kufaishi H, Lye S, Drutz H and Shynlova O: Expression of extracellular matrix-remodeling proteins is altered in vaginal tissue of premenopausal women with severe pelvic organ prolapse. Reprod Sci. 21:704–715. 2014. View Article : Google Scholar : PubMed/NCBI
11	de Landsheere L, Blacher S, Munaut C, Nusgens B, Rubod C, Noel A, Foidart JM, Cosson M and Nisolle M: Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse. Int Urogynecol J. 25:1673–1681. 2014. View Article : Google Scholar : PubMed/NCBI
12	Strinic T, Vulic M, Tomic S, Capkun V, Stipic I and Alujevic I: Increased expression of matrix metalloproteinase-1 in uterosacral ligament tissue from women with pelvic organ prolapse. Acta Obstet Gynecol Scand. 89:832–834. 2010. View Article : Google Scholar : PubMed/NCBI
13	Budatha M, Roshanravan S, Zheng Q, Weislander C, Chapman SL, Davis EC, Starcher B, Word RA and Yanagisawa H: Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest. 121:2048–2059. 2011. View Article : Google Scholar : PubMed/NCBI
14	Woodley DT, Krueger GG, Jorgensen CM, Fairley JA, Atha T, Huang Y, Chan L, Keene DR and Chen M: Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone. J Invest Dermatol. 121:1021–1028. 2003. View Article : Google Scholar : PubMed/NCBI
15	Piperi C and Papavassiliou AG: Molecular mechanisms regulating matrix metalloproteinases. Curr Top Med Chem. 12:1095–1112. 2012. View Article : Google Scholar : PubMed/NCBI
16	Dai W, Liang Z, Liu H, Zhao G and Ju C: Lunasin abrogates the expression of matrix metalloproteinases and reduction of type II collagen. Artif Cells Nanomed Biotechnol. 47:3259–3264. 2019. View Article : Google Scholar : PubMed/NCBI
17	Sun B, Zhou L, Wen Y, Wang C, Baer TM, Pera RR and Chen B: Proliferative behavior of vaginal fibroblasts from women with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol. 183:1–4. 2014. View Article : Google Scholar : PubMed/NCBI
18	Taylor HS, Vanden Heuvel GB and Igarashi P: A conserved Hox axis in the mouse and human female reproductive system: Late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 57:1338–1345. 1997. View Article : Google Scholar : PubMed/NCBI
19	Taylor HS, Igarashi P, Olive DL and Arici A: Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 84:1129–1135. 1999. View Article : Google Scholar : PubMed/NCBI
20	Connell KA, Guess MK, Chen H, Andikyan V, Bercik R and Taylor HS: HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. J Clin Invest. 118:1050–1055. 2008.PubMed/NCBI
21	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 : PubMed/NCBI
22	Ma Y, Guess M, Datar A, Hennessey A, Cardenas I, Johnson J and Connell KA: Knockdown of Hoxa11 in vivo in the uterosacral ligament and uterus of mice results in altered collagen and matrix metalloproteinase activity. Biol Reprod. 86:1002012. View Article : Google Scholar : PubMed/NCBI
23	Wen Y, Polan ML and Chen B: Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence? Hum Reprod. 21:1266–1273. 2006. View Article : Google Scholar : PubMed/NCBI
24	Meijerink AM, van Rijssel RH and van der Linden PJ: Tissue composition of the vaginal wall in women with pelvic organ prolapse. Gynecol Obstet Invest. 75:21–27. 2013. View Article : Google Scholar : PubMed/NCBI
25	Emmerson S, Mukherjee S, Melendez-Munoz J, Cousins F, Edwards SL, Karjalainen P, Ng M, Tan KS, Darzi S, Bhakoo K, et al: Composite mesh design for delivery of autologous mesenchymal stem cells influences mesh integration, exposure and biocompatibility in an ovine model of pelvic organ prolapse. Biomaterials. 225:1194952019. View Article : Google Scholar : PubMed/NCBI
26	Elneil S: Complex pelvic floor failure and associated problems. Best Pract Res Clin Gastroenterol. 23:555–573. 2009. View Article : Google Scholar : PubMed/NCBI
27	Lee UJ, Kerkhof MH, van Leijsen SA and Heesakkers JP: Obesity and pelvic organ prolapse. Curr Opin Urol. 27:428–434. 2017. View Article : Google Scholar : PubMed/NCBI
28	Qiu J, Qin M, Fan B and Chen X: Klotho protein reduced the expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) in fibroblasts from patients with pelvic organ prolapse (POP) by Down-regulating the phosphorylation of ERK1/2. Med Sci Monit. 25:3815–3824. 2019. View Article : Google Scholar : PubMed/NCBI
29	Zeng C, Liu J, Wang H, Zhou Y, Wu J and Yan G: Correlation between autophagy and collagen deposition in patients with pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 24:213–221. 2018. View Article : Google Scholar : PubMed/NCBI
30	Lachowski D, Cortes E, Rice A, Pinato D, Rombouts K and Del Rio Hernandez A: Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis. Sci Rep. 9:72992019. View Article : Google Scholar : PubMed/NCBI
31	Dökmeci F, Tekşen F, Çetinkaya ŞE, Özkan T, Kaplan F and Köse K: Expressions of homeobox, collagen and estrogen genes in women with uterine prolapse. Eur J Obstet Gynecol Reprod Biol. 26–29. 2019. View Article : Google Scholar
32	Wang S, Lu D, Zhang Z, Jia X and Yang L: Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse. PLoS One. 13:e01934562018. View Article : Google Scholar : PubMed/NCBI
33	Makker A, Goel MM, Nigam D, Bhatia V, Mahdi AA, Das V and Pandey A: Endometrial expression of homeobox genes and cell adhesion molecules in infertile women with intramural fibroids during window of implantation. Reprod Sci. 24:435–444. 2017. View Article : Google Scholar : PubMed/NCBI
34	Cunha GR, Robboy SJ, Kurita T, Isaacson D, Shen J, Cao M and Baskin LS: Development of the human female reproductive tract. Differentiation. 103:46–65. 2018. View Article : Google Scholar : PubMed/NCBI
35	Nigdelioglu R, Hamanaka RB, Meliton AY, O'Leary E, Witt LJ, Cho T, Sun K, Bonham C, Wu D, Woods PS, et al: Transforming growth factor (TGF)-β promotes de novo serine synthesis for collagen production. J Biol Chem. 291:27239–27251. 2016. View Article : Google Scholar : PubMed/NCBI
36	Leegant A, Zuckerwise LC, Downing K, Brouwer-Visser J, Zhu C, Cossio MJ, Strube F, Xie X, Banks E and Huang GS: Transforming growth factor β1 and extracellular matrix protease expression in the uterosacral ligaments of patients with and without pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 21:53–58. 2015. View Article : Google Scholar : PubMed/NCBI
37	Ventura RD, Padalhin AR, Park CM and Lee BT: Enhanced decellularization technique of porcine dermal ECM for tissue engineering applications. Mater Sci Eng C Mater Biol Appl. 104:1098412019. View Article : Google Scholar : PubMed/NCBI
38	Zhang Y, He RQ, Dang YW, Zhang XL, Wang X, Huang SN, Huang WT, Jiang MT, Gan XN, Xie Y, et al: Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells. Cancer Cell Int. 16:892016. View Article : Google Scholar : PubMed/NCBI