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Vol. 64 No. 5: Issue 5

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Expression of extracellular matrix and adhesion proteins in pelvic organ prolapse

https://doi.org/10.14715/cmb/2018.64.5.24
Monica Cecati
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Alessandra Corradetti
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Davide Sartini
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Valentina Pozzi
New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Stefano R Giannubilo
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Franca Saccucci
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Andrea Ciavattini
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy
Monica Emanuelli
Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy

Corresponding Author(s) : Monica Emanuelli

m.emanuelli@univpm.it

Cellular and Molecular Biology, Vol. 64 No. 5: Issue 5

Abstract

Pelvic organ prolapse (POP) is a common disorder in women. It is characterized by the descent of the vaginal wall with consequent drop of pelvic organs. Pregnancy, labour and childbirth seem to be important events leading to the development of POP, since they are associated with prolonged stretch and mechanical stress of muscles, ligaments and connective tissue supporting pelvic organs. In pubocervical fascia, we explored the expression level of extracellular matrix and adhesion molecules. Tissue samples were obtained from twenty patients with POP who underwent cystocele repair, and from twenty control subjects during hysterectomy surgery. The PCR array analysis was performed and data were confirmed by Real-Time PCR and Western Blot.  Real-Time PCR results showed a significant upregulation for extracellular matrix protein 1 (ECM1) and integrin beta 3 (ITGB3) and a significant downregulation for FBLN5 in POP group. The decreased mRNA expression of FBLN5 in pathological samples was paralleled by a quantitative decrease in the corresponding protein, as Western Blot test highlighted. Our data provide an understanding of molecular mechanisms involved in POP-related pathophysiological processes and might represent an important tool to develop novel therapeutic agents for the treatment of this condition.

Keywords

Adhesion molecules Imbalanced expression level Pelvic organ prolapse Real-Time PCR.
Cecati, M., Corradetti, A., Sartini, D., Pozzi, V., Giannubilo, S. R., Saccucci, F., Ciavattini, A., & Emanuelli, M. (2018). Expression of extracellular matrix and adhesion proteins in pelvic organ prolapse. Cellular and Molecular Biology, 64(5), 142–148. https://doi.org/10.14715/cmb/2018.64.5.24
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References
  1. References
  2. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997; 89: 501-6. [PubMed: 9083302]
  3. Brown JS, Waetjen LE, Subak LL, Thom DH, Van den Eeden S, Vittinghoff E. Pelvic organ prolapse surgery in the United States, 1997. Am J Obstet Gynecol 2002; 186: 712-6. [PubMed: 11967496]
  4. Mant J, Painter R, Vessey M. Epidemiology of genital prolapse: observations from the Oxford Family Planning Association Study. Br J Obstet Gynaecol 1997; 104: 579-85. [PubMed: 9166201]
  5. Progetto Menopausa Italia Study Group. Risk factors for genital prolapse in non-hysterectomized women around menopause. Results from a large cross-sectional study in menopausal clinics in Italy. Eur J Obstet Gynecol Reprod Biol 2000; 93: 135-40. [PubMed: 11074133]
  6. Rahn DD, Ruff MD, Brown SA, Tibbals HF, Word RA. Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse. Am J Obstet Gynecol 2008; 198: 590. e1-6. [PubMed: 18455541]
  7. Phillips CH, Anthony F, Benyon C, Monga AK. Collagen metabolism in the uterosacral ligaments and vaginal skin of women with uterine prolapse. BJOG 2006; 113: 39-46. [PubMed: 16398770]
  8. Samuelsson EC, Victor FT, Tibblin G, Svärdsudd KF. Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. Am J Obstet Gynecol 1999; 180: 299-305. [PubMed: 9988790]
  9. Drewes PG, Yanagisawa H, Starcher B, Hornstra I, Csiszar K, Marinis SI, et al. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol 2007; 170: 578-89. [PubMed: 17255326]
  10. Jundt K, Kiening M, Fischer P, Bergauer F, Rauch E, Janni W, et al. Is the histomorphological concept of the female pelvic floor and its changes due to age and vaginal delivery correct? Neurourol Urodyn 2005; 24: 44-50. [PubMed: 15573382]
  11. Dietz HP, Jarvis SK, Vancaillie TG. The assessment of levator muscle strength: a validation of three ultrasound techniques. Int Urogynecol J Pelvic Floor Disfunct 2002; 13: 156-9. [PubMed: 12140708]
  12. Koelbl H, Strassegger H, Riss PA, Gruber H. Morphologic and functional aspects of pelvic floor muscles in patients with pelvic relaxation and genuine stress incontinence. Obstet Gynecol 1989; 74: 789-95. [PubMed: 2682414]
  13. Helt M, Benson JT, Russell B, Brubaker L. Levator ani muscle in women with genitourinary prolapse: indirect assessment by muscle histopathology. Neurourol Urodyn 1996; 15: 17-29. [PubMed: 8696353]
  14. DeLancey JO. Anatomy and biomechanics of genital prolapse. Clin Obstet Gynecol 1993; 36: 897-909. [PubMed: 8293591]
  15. Brizzolara SS, Killeen J, Urschitz J. Gene expression profile in pelvic organ prolapse. Mol Hum reprod 2009; 15: 59-67. [PubMed: 19056808]
  16. Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 2002; 187: 56-63. [PubMed: 12114889]
  17. Boreham MK, Miller RT, Schaffer JI, Word RA. Smooth muscle myosin heavy chain and caldesmon expression in the anterior vaginal wall of women with and without pelvic organ prolapse. Am J Obstet Gynecol 2001; 185: 944-52. [PubMed: 11641683]
  18. Moalli PA, Klingensmith WL, Meyn LA, Zyczynski HM. Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor. Am J Obstet Gynecol 2002; 187: 72-9. [PubMed: 12114891]
  19. Jack GS, Nikolova G, Vilain E, Raz S, Rodriguez LV. Familial transmission of genitovaginal prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2006; 17: 498-501. [PubMed: 16365693]
  20. Twiss C, Triaca V, Rodrí­guez LV. Familial transmission of urogenital prolapse and incontinence. Curr Opin Obstet Gynecol 2007; 19: 464-8. [PubMed: 17885463]
  21. Rortveit G, Brown JS, Thom DH, Van Den Eeden SK, Creasman JM, Subak LL. Symptomatic pelvic organ prolapse: prevalence and risk factors in a population-based, racially diverse cohort. Obstet Gynecol 2007; 109: 1396-403. [PubMed: 17540813]
  22. Ferrell G, Lu M, Stoddard P, Sammel MD, Romero R, Strauss JF 3rd, et al. A single nucleotide polymorphism in the promoter of the LOXL1 gene and its relationship to pelvic organ prolapse and preterm premature rupture of membranes. Reprod Sci 2009; 16: 438-46. [PubMed: 19182211]
  23. Hansell NK, Dietz HP, Treloar SA, Clarke B, Martin NG. Genetic covariation of pelvic organ and elbow mobility in twins and their sisters. Twin Res 2004; 7: 254-60. [PubMed: 15193170]
  24. Alperin M, Moalli PA. Remodeling of vaginal connective tissue in patients with prolapse. Curr Opin Obstet Gynecol 2006; 18: 544-50. [PubMed: 16932050]
  25. Goepel C. Differential elastin and tenascin immunolabeling in the uterosacral ligaments in postmenopausal women with and without pelvic organ prolapse. Acta Histochem 2008; 110: 204-9. [PubMed: 18155129]
  26. Strinic T, Vulic M, Tomic S, Capkun V, Stipic I, Alujevic I. Matrix metalloproteinases-1, -2 expression in uterosacral ligaments from women with pelvic organ prolapse. Maturitas 2009; 64: 132-5. [PubMed: 19765922]
  27. Gabriel B, Watermann D, Hancke K, Gitsch G, Werner M, Tempfer C, et al. Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2006; 17: 478-82. [PubMed: 16341461]
  28. Altman D, Forsman M, Falconer C, Lichtenstein P. Genetic influence on stress urinary incontinence and pelvic organ prolapse. Eur Urol 2008; 54: 918-22. [PubMed: 18155350]
  29. Baden WF, Walker TA, Lindsey JH. The vaginal profile. Tex Med. 1968; 64: 56-8. [PubMed: 5653447]
  30. DeLancey JO, Morgan DM, Fenner DE, Kearney R, Guire K, Miller JM, et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol 2007; 109: 295-302. [PubMed: 17267827]
  31. Lei L, Song Y, Chen R. Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal women. Int Urogynecol J Pelvic Floor Dysfunct 2007; 18: 603-7. [PubMed: 17024520]
  32. Goh JT. Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal women. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 76-9. [PubMed: 12054186]
  33. Cosson M, Lambaudie E, Boukerrou M, Lobry P, Crépin G, Ego A. A biomechanical study of the strength of vaginal tissues. Results on 16 post-menopausal patients presenting with genital prolapse. Eur J Obstet Gynecol Reprod Biol 2004; 112: 201-5. [PubMed: 14746960]
  34. Visco AG, Yuan L. Differential gene expression in pubococcygeus muscle from patients with pelvic organ prolapse. Am J Obstet Gynecol 2003; 189: 102-12. [PubMed: 12861146]
  35. 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: 22-9. [PubMed: 16126751]
  36. Ewies AA, Elshafie M, Li J, Stanley A, Thompson J, Styles J, et al. Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene. Mol Hum Reprod 2008; 14: 127-35. [PubMed: 18184756]
  37. Söderberg MW, Byström B, Kalamajski S, Malmström A, Ekman-Ordeberg G. Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse. Mol Hum Reprod 2009; 15: 251-7. [PubMed: 19251763]
  38. Kuang PP, Joyce-Brady M, Zhang XH, Jean JC, Goldstein RH. Fibulin-5 gene expression in human lung fibroblasts is regulated by TGF-beta and phosphatidylinositol 3-kinase activity. Am J Physiol Cell Physiol 2006; 291: C1412-C21. [PubMed: 16837650]
  39. Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA, et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 2002; 415: 168-71. [PubMed: 11805834]
  40. Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 2002; 415: 171-5. [PubMed: 11805835]
  41. Anderson JE, Liu L, Kardami E, Murphy LJ. The pituitary-muscle axis in mdx dystrophic mice. J Neurol Sci 1994; 123: 80-7. [PubMed: 8064326]
  42. Woodard AS, Garcí­a-Cardeña G, Leong M, Madri JA, Sessa WC, Languino LR. The synergistic activity of alphavbeta3 integrin and PDGF receptor increases cell migration. J Cell Sci 1998; 111: 469-78. [PubMed: 9443896]
  43. Akiyama SK. Integrins in cell adhesion and signaling. Hum Cell 1996; 9: 181-6. [PubMed: 9183647]
  44. Villa-Garcia M, Li L, Riely G, Bray P F. Isolation and characterization of a TATA-less promoter for the human beta 3 integrin gene. Blood 1994; 83: 668-76. [PubMed: 8298129]
  45. Daftary GS, Troy PJ, Bagot CN, Young SL, Taylor HS. Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells. Mol Endocrinol March 2002; 16: 571-9. [PubMed: 11875117]
  46. Toupance S, Brassart B, Rabenoelina F, Ghoneim C, Vallar L, Polette M, et al. Elastin-derived peptides increase invasive capacities of lung cancer cells by post-transcriptional regulation of MMP-2 and uPA. Clin Exp Metastasis 2012; 29: 511-22. [PubMed: 22434583]
  47. Fujimoto N, Terlizzi J, Aho S, Brittingham R, Fertala A, Oyama N, et al. Extracellular matrix protein 1 inhibits the activity of matrix metalloproteinase 9 through high-affinity protein/protein interactions. Exp Dermatol. 2006; 15: 300-7. [Pubmed: 16512877]
  48. Zhang N, Ma D, Wang L, Zhu X, Pan Q, Zhao Y, et al. Insufficient Radiofrequency Ablation Treated Hepatocellular Carcinoma Cells Promote Metastasis by Up-Regulation ITGB3. J Cancer. 201; 8:3742-54.
  49. Rapisarda V, Borghesan M, Miguela V, Encheva V, Snijders AP, Lujambio A, et al. Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway. Cell Rep. 2017; 18: 2480-93.
  50. Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K. Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts. J Immunol 2005; 175: 7708-18. [PubMed: 16301681]
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Author Biography

Valentina Pozzi, New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, Via Ranieri 65, 60131 Ancona, Italy


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