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International Urogynecology Journal

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01-11-2010 | Original Article

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Authors: May Alarab, Maria AT Bortolini, Harold Drutz, Stephen Lye, Oksana Shynlova

Published in: International Urogynecology Journal | Issue 11/2010

Abstract

Introduction and Hypothesis

The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle.

Methods

Total mRNAs and proteins extracted from the vaginal tissue were examined by real-time polymerase chain reaction and immunoblotting, and tissue specimens were analyzed by immunohistochemistry.

Results

The expression of LOX, LOXL1, and LOXL3 genes as well as LOX and LOXL3 proteins were significantly reduced in POP patients (P < 0.05). Immunolocalization of LOX family proteins was confirmed in all vaginal specimens.

Conclusion

We proposed that reduced expression of LOX enzymes may result in defective assembly of pelvic tissues and development of POP.

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Hendrix SL, Clark A, Nygaaard I et al (2002) Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity. Am J Obstet Gynecol 186:1160–1166CrossRefPubMed

Luber KM, Boero S, Choe JY (2001) The demographics of pelvic floor disorders: current observations and future projections. Am J Obstet Gynecol 184:1496–1501CrossRefPubMed

Smith AR, Hosker GL, Warrell DW (1989) The role of partial denervation of the pelvic floor in the aetiology of genitourinary prolapse and stress incontinence of urine: a neurophysiological study. Br J Obstet Gynecol 96:24–28

Swift SE, Tate SB, Nicholas J (2003) Correlation of symptoms with degree of pelvic organ support in a general population of women: what is pelvic organ prolapse? Am J Obstet Gynecol 198:372–377CrossRef

Moalli PA, Jones Ivy S, Meyn LA, Zyczynski HM (2003R) Risk factors associated with pelvic floor disorders in women undergoing surgical repair. Obstet Gynecol 101:869–874CrossRef

Harris RL, Cundiff GW, Coates KW, Bump RC (1998) Urinary incontinence and pelvic organ Prolapse in nulliparous women. Obstet Gynecol 92:951–954CrossRefPubMed

O'Boyle AL, Woodman PJ, O'Boyle JD, Davis GD, Swift SE (2002) Pelvic organ support in nulliparous and nonpregnant women: a case control study. Am J Obstet Gynecol 187:99–102CrossRefPubMed

Norton P, Baker J, Sharp H, Warenski J (1995) Genitourinary prolapse and joint mobility in women. Obstet Gynecol 85(2):225–228CrossRefPubMed

Carley ME, Schaffer J (2000) Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers Danlos syndrome. Am J ObstetGynecol 182(5):1021–1023CrossRef

10.

Chen BH, Wen Y, Polan ML (2004) Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse. Neurourol Urodyn 23:119–126CrossRefPubMed

11.

Liu X, Zhao Y, Pawlyk B, Damaser M, Li T (2006) Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol 168(2):519–528CrossRefPubMed

12.

Kobak W, Lu J, Hardart A, Zhang C, Stanczyk F, Felix JC (2005) Expression of lysyl oxidase and transforming growth factor B2 in women with severe pelvic organ prolapse. J Rep Med 50(11):827–831

13.

Zhang SQ, Zhang LL, Yu H (2008) Expression of elastin, lysyl oxidase and elafin in the cardinal ligament of women with pelvic organ prolapse. Zhonghua Fu Chan Ke Za Zhi 43(9):675–679PubMed

14.

Kagan HM, Li W (2003) Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem 88:660–672CrossRefPubMed

15.

Zhang H, Hu W, Ramirez F (1995) Developmental expression of fibrillin genes suggests heterogeneity of extra-cellular microfibrils. J Cell Biol 129:1165–1176CrossRefPubMed

16.

Nakamura T, Lozano P, Ikeda Y et al (2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415:171–175CrossRefPubMed

17.

Phillips C, Anthony F, Benyon C, Monga A (2006) Collagen metabolism in uterosacral ligaments and vaginal skin of women with uterine prolapse. Br J Obstet Gynecol 113:39–46

18.

Chen B, Wen Y, Zhang Z, Guo Y, Warrington JA, Polan ML (2006) Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women. Hum Reprod 21(1):22–29CrossRefPubMed

19.

Bump RC, Mattiasson A, Bo K et al (1996) The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 175:10–17CrossRefPubMed

20.

Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA (2002) Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 187(1):56–63CrossRefPubMed

21.

Miller M, Vadachkoria S, Luthy DA, Williams MA (2005) Evaluation of housekeeping genes in placental comparative expression studies. Placenta 26:601–607CrossRef

22.

Vandesompele J, De Preter K, Pattyn F et al (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):34CrossRef

23.

Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108CrossRefPubMed

24.

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

25.

Görögh T, Weise JB, Holtmeier C et al (2007) Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma. J Pathol 212(1):74–82CrossRefPubMed

26.

Lee JE, Kim Y (2006) A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity. J Biol Chem 281(49):37282–37290CrossRefPubMed

27.

Borel A, Eichenberger D, Farjanel J et al (2001) Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1. J Biol Chem 276(52):48944–48949CrossRefPubMed

28.

Thomassin L, Werneck CC, Broekelmann TJ et al (2005) The pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem 280(52):42848–42855CrossRefPubMed

29.

Shanley CJ, Gharaee-Kermani M, Sarkar R, Welling TH, Kriegel A, Ford JW, Stanley JC, Phan SH (1997) Transforming growth factor-beta 1 increases lysyl oxidase enzyme activity and mRNA in rat aortic smooth muscle cells. J Vasc Surg 25(3):446–452CrossRefPubMed

30.

Nellaiappan K, Risitano A, Liu G, Nicklas G, Kagan HM (2000) Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. J Cell Biochem 79:576–582CrossRefPubMed

Title: LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse
Authors: May Alarab
Maria AT Bortolini
Harold Drutz
Stephen Lye
Oksana Shynlova
Publication date: 01-11-2010
Publisher: Springer-Verlag
Published in: International Urogynecology Journal / Issue 11/2010
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI: https://doi.org/10.1007/s00192-010-1199-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Abstract

Introduction and Hypothesis

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction and Hypothesis

Methods

Results

Conclusion

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