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LncRNA and mRNA Expression Profiling in the Periurethral Vaginal Wall Tissues of Postmenopausal Women with Stress Urinary Incontinence

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Abstract

Stress urinary incontinence (SUI) is one of the major pelvic floor disorders affecting postmenopausal women. To investigate the lncRNA and mRNA expression profiling of SUI in postmenopausal women, we used a microarray analysis to examine the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the periurethral vaginal wall of postmenopausal women with SUI. A total of 8840 lncRNAs and 7102 mRNAs were dysregulated in the two groups (absolute fold change ≥ 2 and P < 0.05). The expression levels of five randomly selected lncRNAs and mRNAs were validated by quantitative real-time PCR. A functional analysis revealed that several lncRNAs are involved in the lysosome pathway associated with extracellular matrix (ECM) remodeling. In addition, we also found several mRNAs involved in fibroblast pseudopodia formation, fibroblast growth, and the regulation of smooth muscle cell differentiation in the urinary tract. Our study offers essential data regarding differentially expressed lncRNAs and mRNAs and may provide new potential candidates for the study of SUI.

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References

  1. Chen B, Wen Y, Zhang Z, Wang H, Warrington JA, Polan ML. Menstrual phase-dependent gene expression differences in periurethral vaginal tissue from women with stress incontinence. Am J Obstet Gynecol. 2003;189(1):89–97.

    Article  PubMed  Google Scholar 

  2. Huang J, Cheng M, Ding Y, Chen L, Hua K. Modified vaginal dilation rat model for postpartum stress urinary incontinence. J Obstet Gynaecol Res. 2013;39(1):256–63.

    Article  PubMed  Google Scholar 

  3. Huang Q, Jin H, Xie Z, Wang M, Chen J, Zhou Y. The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence. J Int Med Res. 2013;41(4):1242–51.

    Article  CAS  PubMed  Google Scholar 

  4. Shamliyan TA, Kane RL, Wyman J, Wilt TJ. Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women. Ann Intern Med. 2008;148(6):459–73.

    Article  PubMed  Google Scholar 

  5. Hunskaar S, Lose G, Sykes D, Voss S. The prevalence of urinary incontinence in women in four European countries. BJU Int. 2004;93(3):324–30.

    Article  CAS  PubMed  Google Scholar 

  6. Diokno AC, Burgio K, Fultz n H, Kinchen KH, Obenchain R, Bump RC. Prevalence and outcomes of continence surgery in community dwelling women. J Urol. 2003;170(2 Pt 1):507–11.

    Article  PubMed  Google Scholar 

  7. Thom DH, van den Eeden SK, Brown JS. Evaluation of parturition and other reproductive variables as risk factors for urinary incontinence in later life. Obstet Gynecol. 1997;90(6):983–9.

    Article  CAS  PubMed  Google Scholar 

  8. Graham CA, Mallett VT. Race as a predictor of urinary incontinence and pelvic organ prolapse. Am J Obstet Gynecol. 2001;185(1):116–20.

    Article  CAS  PubMed  Google Scholar 

  9. Buchsbaum GM, Chin M, Glantz C, Guzick D. Prevalence of urinary incontinence and associated risk factors in a cohort of nuns. Obstet Gynecol. 2002;100(2):226–9.

    PubMed  Google Scholar 

  10. Mushkat Y, Bukovsky I, Langer R. Female urinary stress incontinence--does it have familial prevalence? Am J Obstet Gynecol. 1996;174(2):617–9.

    Article  CAS  PubMed  Google Scholar 

  11. Hannestad YS, Lie RT, Rortveit G, Hunskaar S. Familial risk of urinary incontinence in women: population based cross sectional study. BMJ. 2004;329(7471):889–91.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ertunc D, Tok EC, Pata O, Dilek U, Ozdemir G, Dilek S. Is stress urinary incontinence a familial condition? Acta Obstet Gynecol Scand. 2004;83(10):912–6.

    Article  PubMed  Google Scholar 

  13. Benassi L, Bocchialini E, Bertelli M, Kaihura CT, Ricci L, Siliprandi V. Risk of genital prolapse and urinary incontinence due to pregnancy and delivery. A prospective study. Minerva Ginecol. 2002;54(4):317–24.

    CAS  PubMed  Google Scholar 

  14. Peyrat L, Haillot O, Bruyere F, Boutin JM, Bertrand P, Lanson Y. Prevalence and risk factors of urinary incontinence in young and middle-aged women. BJU Int. 2002;89(1):61–6.

    Article  CAS  PubMed  Google Scholar 

  15. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1):7–21.

    Article  CAS  PubMed  Google Scholar 

  17. Li L, Chang HY. Physiological roles of long noncoding RNAs: insight from knockout mice. Trends Cell Biol. 2014;24(10):594–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.

    Article  CAS  PubMed  Google Scholar 

  19. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.

    Article  CAS  PubMed  Google Scholar 

  20. Lee JT. Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev. 2009;23(16):1831–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472(7341):120–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143(1):46–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Guil S, Esteller M. Cis-acting noncoding RNAs: friends and foes. Nat Struct Mol Biol. 2012;19(11):1068–75.

    Article  CAS  PubMed  Google Scholar 

  24. Szymanski M, Barciszewska MZ, Erdmann VA, Barciszewski J. A new frontier for molecular medicine: noncoding RNAs. Biochim Biophys Acta. 2005;1756(1):65–75.

    CAS  PubMed  Google Scholar 

  25. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xu G, Chen J, Pan Q, Huang K, Pan J, Zhang W, et al. Long noncoding RNA expression profiles of lung adenocarcinoma ascertained by microarray analysis. PLoS One. 2014;9(8):e104044.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Yang M, Tian J, Guo X, Yang Y, Guan R, Qiu M, et al. Long noncoding RNA are aberrantly expressed in human papillary thyroid carcinoma. Oncol Lett. 2016;12(1):544–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Latif S, Bauer-Sardina I, Ranade K, Livak KJ, Kwok PY. Fluorescence polarization in homogeneous nucleic acid analysis II: 5′-nuclease assay. Genome Res. 2001;11(3):436–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Villegas VE, Zaphiropoulos PG. Neighboring gene regulation by antisense long non-coding RNAs. Int J Mol Sci. 2015;16(2):3251–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nygaard I. Urinary incontinence: is cesarean delivery protective? Semin Perinatol. 2006;30(5):267–71.

    Article  PubMed  Google Scholar 

  31. Goldberg RP, Abramov Y, Botros S, Miller JJ, Gandhi S, Nickolov A, et al. Delivery mode is a major environmental determinant of stress urinary incontinence: results of the Evanston-Northwestern Twin Sisters Study. Am J Obstet Gynecol. 2005;193(6):2149–53.

    Article  PubMed  Google Scholar 

  32. Dietz HP, Hansell NK, Grace ME, Eldridge AM, Clarke B, Martin NG. Bladder neck mobility is a heritable trait. BJOG. 2005;112(3):334–9.

    Article  CAS  PubMed  Google Scholar 

  33. Isali I, Mahran A, Khalifa AO, Sheyn D, Neudecker M, Qureshi A, et al. Gene expression in stress urinary incontinence: a systematic review. Int Urogynecol J. 2019.

  34. Diokno AC, Brock BM, Herzog AR, Bromberg J. Medical correlates of urinary incontinence in the elderly. Urology. 1990;36(2):129–38.

    Article  CAS  PubMed  Google Scholar 

  35. Knapp TR, Nickel JT. Re: ‘Factors associated with risk of stress urinary incontinence in women’. Nurs Res. 1995;44(1):58.

    Article  CAS  PubMed  Google Scholar 

  36. Altman D, Forsman M, Falconer C, Lichtenstein P. Genetic influence on stress urinary incontinence and pelvic organ prolapse. Eur Urol. 2008;54(4):918–22.

    Article  PubMed  Google Scholar 

  37. Nygaard IE, Heit M. Stress urinary incontinence. Obstet Gynecol. 2004;104(3):607–20.

    Article  PubMed  Google Scholar 

  38. Davidson JM. Biochemistry and turnover of lung interstitium. Eur Respir J. 1990;3(9):1048–63.

    CAS  PubMed  Google Scholar 

  39. Chen Y, DeSautel M, Anderson A, Badlani G, Kushner L. Collagen synthesis is not altered in women with stress urinary incontinence. Neurourol Urodyn. 2004;23(4):367–73.

    Article  PubMed  CAS  Google Scholar 

  40. Chen BH, Wen Y, Li H, Polan ML. Collagen metabolism and turnover in women with stress urinary incontinence and pelvic prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2002;13(2):80–7 discussion 87.

    Article  CAS  PubMed  Google Scholar 

  41. Lucey EC, Goldstein RH, Stone PJ, Snider GL. Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. Am J Respir Crit Care Med. 1998;158(2):555–64.

    Article  CAS  PubMed  Google Scholar 

  42. Vlahovic G, Russell ML, Mercer RR, Crapo JD. Cellular and connective tissue changes in alveolar septal walls in emphysema. Am J Respir Crit Care Med. 1999;160(6):2086–92.

    Article  CAS  PubMed  Google Scholar 

  43. Lim VF, Khoo JK, Wong V, Moore KH. Recent studies of genetic dysfunction in pelvic organ prolapse: the role of collagen defects. Aust N Z J Obstet Gynaecol. 2014;54(3):198–205.

    Article  PubMed  Google Scholar 

  44. Hirsch DS, Pirone DM, Burbelo PD. A new family of Cdc42 effector proteins, CEPs, function in fibroblast and epithelial cell shape changes. J Biol Chem. 2001;276(2):875–83.

    Article  CAS  PubMed  Google Scholar 

  45. Sangsawang B. Risk factors for the development of stress urinary incontinence during pregnancy in primigravidae: a review of the literature. Eur J Obstet Gynecol Reprod Biol. 2014;178:27–34.

    Article  PubMed  Google Scholar 

  46. Chen B, Wen Y, Zhang Z, Guo Y, Warrington JA, Polan ML. Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women. Hum Reprod. 2006;21(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  47. Liu X, Lang J, Wu S, Cheng L, Wang W, Zhu L. Differential expression of microRNAs in periurethral vaginal wall tissues of postmenopausal women with and without stress urinary incontinence. Menopause. 2014;21(10):1122–8.

    Article  PubMed  Google Scholar 

  48. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen YS, Wang XJ, Feng W, Hua KQ. Advanced glycation end products decrease collagen I levels in fibroblasts from the vaginal wall of patients with POP via the RAGE, MAPK and NF-kappaB pathways. Int J Mol Med. 2017;40(4):987–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Falconer C, Ekman G, Malmstrom A, Ulmsten U. Decreased collagen synthesis in stress-incontinent women. Obstet Gynecol. 1994;84(4):583–6.

    CAS  PubMed  Google Scholar 

  51. Liu X, Wang S, Wu S, Hao Q, Li Y, Guo Z, et al. Exosomes secreted by adipose-derived mesenchymal stem cells regulate type I collagen metabolism in fibroblasts from women with stress urinary incontinence. Stem Cell Res Ther. 2018;9(1):159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Luzio JP, Pryor PR, Bright NA. Lysosomes: fusion and function. Nat Rev Mol Cell Biol. 2007;8(8):622–32.

    Article  CAS  PubMed  Google Scholar 

  53. Bailey AJ. Perspective article: the fate of collagen implants in tissue defects. Wound Repair Regen. 2000;8(1):5–12.

    Article  CAS  PubMed  Google Scholar 

  54. Padamsey Z, McGuinness L, Bardo SJ, Reinhart M, Tong R, Hedegaard A, et al. Activity-dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines. Neuron. 2017;93(1):132–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We would like to thank American Journal Experts (https://www.aje.com/) for English language editing.

Funding

This work was financially supported by the Science and Technology Development Fund of Nanjing Medical University (2015NJMUZD061, NMUB2018258) and Scientific Research Development Fund of Kangda College, Nanjing Medical University (KD2018KYJJZD003).

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Author notes

  1. Aimin Wei and Ruohan Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Affiliated Obstetrics and Gynecology Hospital, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China

    Aimin Wei, Chencheng Dai, Pengfei Xu, Juan Xu & Hui Tang

  2. The First Clinical Medical College, Nanjing Medical University, Nanjing, 211166, China

    Ruohan Wang

  3. Kangda College of Nanjing Medical University, Lianyungang, 222002, China

    Kai Wei, Yue Huang & Yan Zhang

  4. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, 211166, China

    Yun Fan

  5. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Yun Fan

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  1. Aimin Wei
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Contributions

YF and YZ directed the study and were responsible for study design. AMW and RHW performed overall project management with KW. CCD and YH performed data analysis with PFX and drafted the initial manuscript. JX and HT were responsible for subject recruitment and sample preparation. All authors read and approved the final manuscript.

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Correspondence to Yan Zhang or Yun Fan.

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The authors declare that they have no competing interests.

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This study was approved by the Research Ethics Committee of Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University (Nanjing, China).

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Wei, A., Wang, R., Wei, K. et al. LncRNA and mRNA Expression Profiling in the Periurethral Vaginal Wall Tissues of Postmenopausal Women with Stress Urinary Incontinence. Reprod. Sci. 27, 1490–1501 (2020). https://doi.org/10.1007/s43032-020-00144-3

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