Vol 56, No 3 (2018)
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Published online: 2018-08-29

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Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium

Barbara Grzechocinska1, Filip A. Dabrowski1, Anna Cyganek1, Marcin Chlebus2, Christopher Kobierzycki3, Lukasz Michalowski4, Barbara Gornicka4, Miroslaw Wielgos1
Pubmed: 30187906
Folia Histochem Cytobiol 2018;56(3):133-140.

Abstract

Introduction. Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle.
Material and methods. The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model.
Results. Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed.
Conclusions. The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.
 

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References

  1. Ishikawa T, Harada T, Kubota T, et al. Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro. Reproduction. 2007; 133(6): 1233–1239.
  2. Vassilev V, Pretto CM, Cornet PB, et al. Response of matrix metalloproteinases and tissue inhibitors of metalloproteinases messenger ribonucleic acids to ovarian steroids in human endometrial explants mimics their gene- and phase-specific differential control in vivo. J Clin Endocrinol Metab. 2005; 90(10): 5848–5857.
  3. Konac E, Alp E, Onen HI, et al. Endometrial mRNA expression of matrix metalloproteinases, their tissue inhibitors and cell adhesion molecules in unexplained infertility and implantation failure patients. Reprod Biomed Online. 2009; 19(3): 391–397.
  4. Theocharis AD, Skandalis SS, Gialeli C, et al. Extracellular matrix structure. Adv Drug Deliv Rev. 2016; 97: 4–27.
  5. Stettner R, Bogusiewicz M, Rechberger T. [Matrix metalloproteinases and their inhibitors in ovarian cancer progression--diagnostic and therapeutic implications]. Ginekol Pol. 2009; 80(1): 47–53.
  6. O'Sullivan S, Medina C, Ledwidge M, et al. Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance-NO and MMP-9 interactions. Biochim Biophys Acta. 2014; 1843(3): 603–617.
  7. Wrzyszcz A, Wozniak M. On the origin of matrix metalloproteinase-2 and -9 in blood platelets. Platelets. 2012; 23(6): 467–474.
  8. DeCoux A, Lindsey ML, Villarreal F, et al. Myocardial matrix metalloproteinase-2: inside out and upside down. J Mol Cell Cardiol. 2014; 77: 64–72.
  9. Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016; 31(sup1): 177–183.
  10. Noguchi Y, Sato T, Hirata M, et al. Identification and characterization of extracellular matrix metalloproteinase inducer in human endometrium during the menstrual cycle in vivo and in vitro. J Clin Endocrinol Metab. 2003; 88(12): 6063–6072.
  11. Kaneshiro B, Edelman A, Dash C, et al. Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity. Contraception. 2016; 93(1): 65–69.
  12. Szymanowski K, Mikołajczyk M, Wirstlein P, et al. Matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinases (TIMP-1) and transforming growth factor-β2 (TGF-β2) expression in eutopic endometrium of women with peritoneal endometriosis. Ann Agric Environ Med. 2016; 23(4): 649–653.
  13. Goffin F, Munaut C, Frankenne F, et al. Expression pattern of metalloproteinases and tissue inhibitors of matrix-metalloproteinases in cycling human endometrium. Biol Reprod. 2003; 69(3): 976–984.
  14. Isaka K, Nishi H, Nakai H, et al. Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma. Cancer. 2003; 97(1): 79–89.
  15. Yanaihara A, Otsuka Y, Iwasaki S, et al. Comparison in gene expression of secretory human endometrium using laser microdissection. Reprod Biol Endocrinol. 2004; 2: 66.
  16. Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol. 2015; 44-46: 247–254.
  17. Skrzypczak J, Wirstlein P, Mikołajczyk M, et al. TGF superfamily and MMP2, MMP9, TIMP1 genes expression in the endometrium of women with impaired reproduction. Folia Histochem Cytobiol. 2007; 45 Suppl 1: S143–S148.
  18. Nagase H, Woessner J. Matrix Metalloproteinases. Journal of Biological Chemistry. 1999; 274(31): 21491–21494.
  19. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3): 562–573.
  20. Vincent AJ, Zhang J, Ostör A, et al. Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding? Hum Reprod. 2002; 17(5): 1189–1198.
  21. Bogusiewicz M, Stryjecka-Zimmer M, Postawski K, et al. Activity of matrix metalloproteinase-2 and -9 and contents of their tissue inhibitors in uterine leiomyoma and corresponding myometrium. Gynecol Endocrinol. 2007; 23(9): 541–546.
  22. Wilczek E, Rzepko R, Nowis D, et al. The possible role of factor H in colon cancer resistance to complement attack. Int J Cancer. 2008; 122(9): 2030–2037.
  23. Grzechocińska B, Dąbrowski F, Cyganek A, et al. The role of metalloproteinases in endometrial remodelling during menstrual cycle. Ginekol Pol. 2017; 88(6): 337–342.
  24. Guccione M, Silbiger S, Lei J, et al. Estradiol upregulates mesangial cell MMP-2 activity via the transcription factor AP-2. Am J Physiol Renal Physiol. 2002; 282(1): F164–F169.
  25. Wingrove CS, Garr E, Godsland IF, et al. 17beta-oestradiol enhances release of matrix metalloproteinase-2 from human vascular smooth muscle cells. Biochim Biophys Acta. 1998; 1406(2): 169–174.
  26. Huang HF, Hong LH, Tan Yi, et al. Matrix metalloproteinase 2 is associated with changes in steroid hormones in the sera and peritoneal fluid of patients with endometriosis. Fertil Steril. 2004; 81(5): 1235–1239.
  27. Furukawa Y, Kawano Y, Fukuda J, et al. The production of vascular endothelial growth factor and metalloproteinase via protease-activated receptor in human endometrial stromal cells. Fertil Steril. 2009; 91(2): 535–541.
  28. Evron A, Goldman S, Shalev E. Effect of primary human endometrial stromal cells on epithelial cell receptivity and protein expression is dependent on menstrual cycle stage. Hum Reprod. 2011; 26(1): 176–190.
  29. Kronenberg HM, Larsen PR, Melmed S, et al. Williams textbook of endocrinology. 12th ed Philadelphia: Elsevier; 2011 xviii. ; 1897: sivua.
  30. Itoh H, Kishore AH, Lindqvist A, et al. Transforming growth factor β1 (TGFβ1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells. J Clin Endocrinol Metab. 2012; 97(6): E888–E897.
  31. Irwin JC, Kirk D, Gwatkin RB, et al. Human endometrial matrix metalloproteinase-2, a putative menstrual proteinase. Hormonal regulation in cultured stromal cells and messenger RNA expression during the menstrual cycle. J Clin Invest. 1996; 97(2): 438–447.
  32. Zhang J, Hampton AL, Nie G, et al. Progesterone inhibits activation of latent matrix metalloproteinase (MMP)-2 by membrane-type 1 MMP: enzymes coordinately expressed in human endometrium. Biol Reprod. 2000; 62(1): 85–94.
  33. Brenner RM, Slayden OvD. Molecular and functional aspects of menstruation in the macaque. Rev Endocr Metab Disord. 2012; 13(4): 309–318.
  34. Collier IE, Wilhelm SM, Eisen AZ, et al. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988; 263(14): 6579–6587.
  35. Berton A, Selvais C, Lemoine P, et al. Binding of matrilysin-1 to human epithelial cells promotes its activity. Cell Mol Life Sci. 2007; 64(5): 610–620.
  36. Osteen KG, Rodgers WH, Gaire M, et al. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc Natl Acad Sci U S A. 1994; 91(21): 10129–10133.
  37. Rudolph-Owen LA, Slayden OD, Matrisian LM, et al. Matrix metalloproteinase expression in Macaca mulatta endometrium: evidence for zone-specific regulatory tissue gradients. Biol Reprod. 1998; 59(6): 1349–1359.
  38. Curry TE, Osteen KG. Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol Reprod. 2001; 64(5): 1285–1296.
  39. Dong JC, Dong H, Campana A, et al. Matrix metalloproteinases and their specific tissue inhibitors in menstruation. Reproduction. 2002; 123(5): 621–631.
  40. Lockwood CJ. Mechanisms of normal and abnormal endometrial bleeding. Menopause. 2011; 18(4): 408–411.
  41. Määttä M, Soini Y, Liakka A, et al. Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal, hyperplastic, and neoplastic endometrium. Enhanced expression by endometrial adenocarcinomas is associated with low differentiation. Am J Clin Pathol. 2000; 114(3): 402–411.
  42. Rodgers WH, Matrisian LM, Giudice LC, et al. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones. J Clin Invest. 1994; 94(3): 946–953.
  43. Amalinei C, Păvăleanu I, Lozneanu L, et al. Endometriosis - insights into a multifaceted entity. Folia Histochem Cytobiol. 2018; 1(2): 61–82.