Regulation of Uterine Matrix Metalloproteinase-9 and the Role of MicroRNAs

 

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ABSTRACT

Controlled expression of matrix metalloproteinase-9 (MMP9) is vital for normal uterine physiology, whereas abnormal expression of MMP9 is associated with uterine disease. Despite the importance of MMP9 within the uterus, its regulation is poorly understood. In this review, the complex regulation of MMP9 within the uterus is highlighted, and the potential novel role of microRNAs in the regulation of this protease is discussed. Emphasis is placed on the necessity to enhance our understanding of the regulation of MMP9 expression, which may lead to the establishment of novel approaches to counteract misexpression of this protease and the diseases associated with it.

REFERENCES

• 1 Nagase H, Woessner Jr J F. Matrix metalloproteinases.  J Biol Chem. 1999;  274 21491-21494
  CrossrefPubMedGoogle Scholar
• 2 Sternlicht M D, Werb Z. How matrix metalloproteinases regulate cell behavior.  Annu Rev Cell Dev Biol. 2001;  17 463-516
  CrossrefPubMedGoogle Scholar
• 3 Birkedal-Hansen H, Moore W G, Bodden M K et al.. Matrix metalloproteinases: a review.  Crit Rev Oral Biol Med. 1993;  4 197-250
  PubMedGoogle Scholar
• 4 Gomez D E, Alonso D F, Yoshiji H, Thorgeirsson U P. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.  Eur J Cell Biol. 1997;  74 111-122
  PubMedGoogle Scholar
• 5 Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function.  Biochim Biophys Acta. 2000;  1477 267-283
  CrossrefPubMedGoogle Scholar
• 6 Yoshida S, Matsumoto K, Tomioka D et al.. Recombinant hepatocyte growth factor accelerates cutaneous wound healing in a diabetic mouse model.  Growth Factors. 2004;  22 111-119
  CrossrefPubMedGoogle Scholar
• 7 Curry Jr T E, Osteen K G. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle.  Endocr Rev. 2003;  24 428-465
  CrossrefPubMedGoogle Scholar
• 8 Zhang X, Nothnick W B. The role and regulation of the uterine matrix metalloproteinase system in menstruating and non-menstruating species.  Front Biosci. 2005;  10 353-366
  CrossrefPubMedGoogle Scholar
• 9 Bany B M, Harvey M B, Schultz G A. Expression of matrix metalloproteinases 2 and 9 in the mouse uterus during implantation and oil-induced decidualization.  J Reprod Fertil. 2000;  120 125-134
  PubMedGoogle Scholar
• 10 Freitas S, Meduri G, Le Nestour E, Bausero P, Perrot-Applanat M. Expression of metalloproteinases and their inhibitors in blood vessels in human endometrium.  Biol Reprod. 1999;  61 1070-1082
  CrossrefPubMedGoogle Scholar
• 11 Vincent A J, Malakooti N, Zhang J, Rogers P A, Affandi B, Salamonsen L A. Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinases-9 (gelatinase-B).  Hum Reprod. 1999;  14 807-815
  CrossrefPubMedGoogle Scholar
• 12 Jeziorska M, Nagase H, Salamonsen L A, Woolley D E. Immunolocalization of the matrix metalloproteinases gelatinase B and stromelysin 1 in human endometrium throughout the menstrual cycle.  J Reprod Fertil. 1996;  107 43-51
  PubMedGoogle Scholar
• 13 Rawdanowicz T J, Hampton A L, Nagase H, Woolley D E, Salamonsen L A. Matrix metalloproteinase production by cultured human endometrial stromal cells: identification of interstitial collagenase, gelatinase-A, gelatinase-B, and stromelysin-1 and their differential regulation by interleukin-1 alpha and tumor necrosis factor-alpha.  J Clin Endocrinol Metab. 1994;  79 530-536
  CrossrefPubMedGoogle Scholar
• 14 Salamonsen L A, Woolley D E. Matrix metalloproteinases in normal menstruation.  Hum Reprod. 1996;  11(Suppl 2) 124-133
  PubMedGoogle Scholar
• 15 Stygar D, Wang H, Vladic Y S, Ekman G, Eriksson H, Sahlin L. Increased level of matrix metalloproteinases 2 and 9 in the ripening process of the human cervix.  Biol Reprod. 2002;  67 889-894
  CrossrefPubMedGoogle Scholar
• 16 Skinner J L, Riley S C, Gebbie A E, Glasier A F, Critchley H O. Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel.  Hum Reprod. 1999;  14 793-799
  CrossrefPubMedGoogle Scholar
• 17 Hickey M, Higham J, Sullivan M, Miles L, Fraser I S. Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP9) and tissue inhibitors of MMPs.  Fertil Steril. 2001;  75 288-296
  CrossrefPubMedGoogle Scholar
• 18 Vincent A J, Zhang J, Ostor 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 1189-1198
  CrossrefPubMedGoogle Scholar
• 19 Galant C, Berliere M, Dubois D et al.. Focal expression and final activity of matrix metalloproteinases may explain irregular dysfunctional endometrial bleeding.  Am J Pathol. 2004;  165 83-94
  CrossrefPubMedGoogle Scholar
• 20 Chung H W, Wen Y, Chun S H, Nezhat C, Woo B H, Lake Polan M. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium in women with endometriosis: a rationale for endometriotic invasiveness.  Fertil Steril. 2001;  75 152-159
  CrossrefPubMedGoogle Scholar
• 21 Szamatowicz J, Laudanski P, Tomaszewska I. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: a possible role in the pathogenesis of endometriosis.  Hum Reprod. 2002;  17 284-288
  CrossrefPubMedGoogle Scholar
• 22 Collette T, Bellehumeur C, Kats R et al.. Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of matrix metalloproteinase-9.  Hum Reprod. 2004;  19 1257-1264
  CrossrefPubMedGoogle Scholar
• 23 Collette T, Maheux R, Mailloux J, Akoum A. Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis.  Hum Reprod. 2006;  21 3059-3067
  CrossrefPubMedGoogle Scholar
• 24 Inagaki N, Stern C, McBain J, Lopata A, Kornman L, Wilkinson D. Analysis of intra-uterine cytokine concentration and matrix metalloproteinase activity in women with recurrent failed embryo transfer.  Hum Reprod. 2003;  18 608-615
  CrossrefPubMedGoogle Scholar
• 25 Inagaki N, Ung L, Otani T, Wilkinson D, Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.  Eur J Obstet Gynecol Reprod Biol. 2003;  111 197-203
  CrossrefPubMedGoogle Scholar
• 26 Soini Y, Alarakkola E, Autio-Harmainen H. Expression of messenger RNAs for metalloproteinases 2 and 9, type IV collagen, and laminin in non-neoplastic and neoplastic endometrium.  Hum Pathol. 1997;  28 220-226
  CrossrefPubMedGoogle Scholar
• 27 Di Nezza L A, Misajon A, Zhang J et al.. Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion.  Cancer. 2002;  94 1466-1475
  CrossrefPubMedGoogle Scholar
• 28 Lopata A, Agresta F, Quinn M A, Smith C, Ostor A G, Salamonsen L A. Detection of endometrial cancer by determination of matrix metalloproteinases in the uterine cavity.  Gynecol Oncol. 2003;  90 318-324
  CrossrefPubMedGoogle Scholar
• 29 Aglund K, Rauvala M, Puistola U et al.. Gelatinases A and B (MMP-2 and MMP9) in endometrial cancer – MMP9 correlates to the grade and the stage.  Gynecol Oncol. 2004;  94 699-704
  CrossrefPubMedGoogle Scholar
• 30 Kamat A A, Feng S, Agoulnik I U et al.. The role of relaxin in endometrial cancer.  Cancer Biol Ther. 2006;  5 71-77
  PubMedGoogle Scholar
• 31 Chantrain C F, Shimada H, Jodele S et al.. Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment.  Cancer Res. 2004;  64 1675-1686
  CrossrefPubMedGoogle Scholar
• 32 Ueno H, Yamashita K, Azumano I, Inoue M, Okada Y. Enhanced production and activation of matrix metalloproteinase-7 (matrilysin) in human endometrial carcinomas.  Int J Cancer. 1999;  84 470-477
  CrossrefPubMedGoogle Scholar
• 33 Marbaix E, Donnez J, Courtoy P J, Eeckhout Y. Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants.  Proc Natl Acad Sci U S A. 1992;  89 11789-11793
  CrossrefPubMedGoogle Scholar
• 34 Cornet P B, Galant C, Eeckhout Y, Courtoy P J, Marbaix E, Henriet P. Regulation of matrix metalloproteinase-9/gelatinase B expression and activation by ovarian steroids and LEFTY-A/endometrial bleeding-associated factor in the human endometrium.  J Clin Endocrinol Metab. 2005;  90 1001-1011
  PubMedGoogle Scholar
• 35 Van den Steen P E, Dubois B, Nelissen I, Rudd P M, Dwek R A, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP9).  Crit Rev Biochem Mol Biol. 2002;  37 375-536
  CrossrefPubMedGoogle Scholar
• 36 Zhang X, Christenson L K, Nothnick W B. Regulation of MMP9 expression and activity in the mouse uterus by estrogen.  Mol Reprod Dev. 2007;  74 321-331
  CrossrefPubMedGoogle Scholar
• 37 Ambros V. The function of animal microRNAs.  Nature. 2004;  431 350-355
  CrossrefPubMedGoogle Scholar
• 38 Bartel D P. MicroRNAs: genomics, biogenesis, mechanism and function.  Cell. 2004;  116 281-297
  CrossrefPubMedGoogle Scholar
• 39 He L, Hannon G J. MicroRNAs: small RNAs with a big role in gene regulation.  Nat Rev Genet. 2004;  5 522-531
  CrossrefPubMedGoogle Scholar
• 40 Valencia-Sanchez M A, Liu J, Hannon G J, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs.  Genes Dev. 2006;  20 515-524
  CrossrefPubMedGoogle Scholar
• 41 Iorio M V, Ferracin M, Liu C G et al.. MicroRNA gene expression deregulation in human breast cancer.  Cancer Res. 2005;  65 7065-7070
  CrossrefPubMedGoogle Scholar
• 42 Calin G A, Croce C M. MicroRNA-cancer connection: the beginning of a new tale.  Cancer Res. 2006;  66 7390-7394
  CrossrefPubMedGoogle Scholar
• 43 Thomson J M, Newman M, Parker J S, Morin-Kensicki E M, Wright T, Hammond S M. Extensive post-transcriptional regulation of microRNAs and its implications for cancer.  Genes Dev. 2006;  20 2202-2207
  CrossrefPubMedGoogle Scholar
• 44 Saito Y, Liang G, Egger G et al.. Specific activation of microRNA-127 with down regulation of the proto-oncogne BCL6 by chromatin-modifying drugs in human cancer cells.  Cancer Cell. 2006;  9 435-443
  Google Scholar

Warren B NothnickPh.D. 

Associate Professor, Departments of Obstetrics & Gynecology and Molecular & Integrative Physiology, University of Kansas Medical Center

Mail stop 2028, 3901 Rainbow Boulevard, Kansas City, KS 66160

Email: wnothnic@kumc.edu