BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

  • Choi, Hee-Jung (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Park, Mi-Ju (Healthy Aging Korean Medical Research Center, Pusan National University) ;
  • Kim, Bo-Sung (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Choi, Hee-Jin (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Joo, Bosun (Healthy Aging Korean Medical Research Center, Pusan National University) ;
  • Lee, Kyu Sup (Department of Obstetrics & Gynecology, Pusan National University Hospital) ;
  • Choi, Jung-Hye (Department of Life and Nanopharmaceutical Sciences and Department of Oriental Pharmacy, Kyung Hee University) ;
  • Chung, Tae-Wook (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Ha, Ki-Tae (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
  • 투고 : 2017.06.11
  • 심사 : 2017.07.31
  • 발행 : 2017.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. $TGF-{\beta}1$ and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of $TGF-{\beta}1$ on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor ${\beta}1$ ($TGF-{\beta}1$) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, $TGF-{\beta}1$ directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of ${\alpha}V$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ via the activation of the $TGF-{\beta}1/TGF-{\beta}RI/Smad2$ signaling pathway. Conversely, the adhesion of $TGF-{\beta}1-stimulated$ endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific $TGF-{\beta}1-mediated$ integrins ${\alpha}V$, ${\beta}1$, and ${\beta}4$ on the endometrial cell membrane. Taken together, these results suggest that $TGF-{\beta}1$ may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

키워드

참고문헌

  1. Ping S, Ma C, Liu P et al (2016) Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data. Arch Gynecol Obstet 293, 797-804 https://doi.org/10.1007/s00404-015-3875-y
  2. Nothnick W and Alali Z (2016) Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment. F1000Res 5
  3. Bedir R, Sehitoglu I, Balik G et al (2016) The role of the adhesion molecule Nectin-4 in the pathogenesis of endometriosis. Clin Exp Obstet Gynecol 43, 463-466 https://doi.org/10.1016/j.ogc.2016.04.005
  4. Schutt AK, Atkins KA, Slack-Davis JK and Stovall DW (2015) VCAM-1 on peritoneum and alpha4beta1 integrin in endometrium and their implications in endometriosis. Int J Gynecol Pathol 34, 85-89 https://doi.org/10.1097/PGP.0000000000000118
  5. Sundqvist J, Andersson KL, Scarselli G, Gemzell-Danielsson K and Lalitkumar PG (2012) Expression of adhesion, attachment and invasion markers in eutopic and ectopic endometrium: a link to the aetiology of endometriosis. Hum Reprod 27, 2737-2746 https://doi.org/10.1093/humrep/des220
  6. Surrey ES, Minjarez DA and Schoolcraft WB (2007) The incidence of aberrant endometrial alphavbeta(3) vitronectin expression in a high risk infertility population: could prolonged GnRH agonist therapy play a role? J Assist Reprod Genet 24, 553-556 https://doi.org/10.1007/s10815-007-9164-3
  7. Sanchez AM, Quattrone F, Pannese M et al (2017) The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis. Hum Reprod 32, 175-184
  8. Rakhila H, Girard K, Leboeuf M, Lemyre M and Akoum A (2014) Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritonealendometrial tissue interaction in vivo: a plausible link to endometriosis development. PLoS One 9, e110434 https://doi.org/10.1371/journal.pone.0110434
  9. Lee J, Banu SK, Burghardt RC, Starzinski-Powitz A and Arosh JA (2013) Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms. Biol Reprod 88, 77
  10. Khoufache K, Bondza PK, Harir N et al (2012) Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment. Am J Pathol 181, 1197-1205 https://doi.org/10.1016/j.ajpath.2012.06.022
  11. Arici A (2002) Local cytokines in endometrial tissue: the role of interleukin-8 in the pathogenesis of endometriosis. Ann N Y Acad Sci 955, 101-109; discussion 118, 396-406 https://doi.org/10.1111/j.1749-6632.2002.tb02770.x
  12. Garcia-Velasco JA and Arici A (1999) Interleukin-8 expression in endometrial stromal cells is regulated by integrin-dependent cell adhesion. Mol Hum Reprod 5, 1135-1140 https://doi.org/10.1093/molehr/5.12.1135
  13. Omwandho CO, Konrad L, Halis G, Oehmke F and Tinneberg HR (2010) Role of TGF-betas in normal human endometrium and endometriosis. Hum Reprod 25, 101-109 https://doi.org/10.1093/humrep/dep382
  14. Tamura M, Fukaya T, Enomoto A, Murakami T, Uehara S and Yajima A (1999) Transforming growth factor-beta isoforms and receptors in endometriotic cysts of the human ovary. Am J Reprod Immunol 42, 160-167 https://doi.org/10.1111/j.1600-0897.1999.tb00480.x
  15. Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M and Marsico S (2002) Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest 54, 82-87 https://doi.org/10.1159/000067717
  16. D'Hooghe TM, Xiao L and Hill JA (2001) Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis. Arch Obstet 265, 40-44 https://doi.org/10.1007/s004040000126
  17. Dela Cruz C and Reis FM (2015) The role of TGFbeta superfamily members in the pathophysiology of endometriosis. Gynecol Endocrinol 31, 511-515 https://doi.org/10.3109/09513590.2015.1018166
  18. Chegini N (2008) TGF-beta system: the principal profibrotic mediator of peritoneal adhesion formation. Semin Reprod Med 26, 298-312 https://doi.org/10.1055/s-0028-1082388
  19. Sandoval P, Jimenez-Heffernan JA, Guerra-Azcona G et al (2016) Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions. J Pathol 239, 48-59 https://doi.org/10.1002/path.4695
  20. Chin SL, Johnson SA, Quinn J et al (2003) A role for alphaV integrin subunit in TGF-beta-stimulated osteoclastogenesis. Biochem Biophys Res Commun 307, 1051-1058 https://doi.org/10.1016/S0006-291X(03)01294-4
  21. Dou Q, Williams RS and Chegini N (1997) Inhibition of transforming growth factor-beta 1 alters the growth, anchor-dependent cell aggregation and integrin mRNA expression in human promonocytes: implications for endometriosis and peritoneal adhesion formation. Mol Hum Reprod 3, 383-391 https://doi.org/10.1093/molehr/3.5.383
  22. Honda E, Yoshida K and Munakata H (2010) Transforming growth factor-beta upregulates the expression of integrin and related proteins in MRC-5 human myofibroblasts. Tohoku J Exp Med 220, 319-327 https://doi.org/10.1620/tjem.220.319
  23. Moyano JV, Greciano PG, Buschmann MM, Koch M and Matlin KS (2010) Autocrine transforming growth factor-{beta}1 activation mediated by integrin {alpha}V{beta}3 regulates transcriptional expression of laminin-332 in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 21, 3654-3668 https://doi.org/10.1091/mbc.E10-06-0523
  24. Young VJ, Brown JK, Saunders PT, Duncan WC and Horne AW (2014) The peritoneum is both a source and target of TGF-beta in women with endometriosis. PLoS One 9, e106773 https://doi.org/10.1371/journal.pone.0106773
  25. Witz CA, Monotoya-Rodriguez IA and Schenken RS (1999) Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril 71, 56-60 https://doi.org/10.1016/S0015-0282(98)00400-2
  26. Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE and Schenken RS (2002) Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod 17, 2832-2838 https://doi.org/10.1093/humrep/17.11.2832
  27. Witz CA, Thomas MR, Montoya-Rodriguez IA, Nair AS, Centonze VE and Schenken RS (2001) Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril 75, 385-390 https://doi.org/10.1016/S0015-0282(00)01699-X
  28. Lucidi RS, Witz CA, Chrisco M, Binkley PA, Shain SA and Schenken RS (2005) A novel in vitro model of the early endometriotic lesion demonstrates that attachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. Fertil Steril 84, 16-21 https://doi.org/10.1016/j.fertnstert.2004.10.058
  29. Young VJ, Brown JK, Saunders PT and Horne AW (2013) The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update 19, 558-569 https://doi.org/10.1093/humupd/dmt024
  30. Campbell ID and Humphries MJ (2011) Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol 3
  31. Merviel P, Challier JC, Carbillon L, Foidart JM and Uzan S (2001) The role of integrins in human embryo implantation. Fetal Diagn Ther 16, 364-371 https://doi.org/10.1159/000053942
  32. Umezawa M, Saito Y, Tanaka-Hattori N, Takeda K, Ihara T and Sugamata M (2012) Expression profile of extracellular matrix and adhesion molecules in the development of endometriosis in a mouse model. Reprod Sci 19, 1365-1372 https://doi.org/10.1177/1933719112450340
  33. Gupta D, Hull ML, Fraser I et al (2016) Endometrial biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev 4, CD012165
  34. Klemmt PA, Carver JG, Koninckx P, McVeigh EJ and Mardon HJ (2007) Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression. Hum Reprod 22, 3139-3147 https://doi.org/10.1093/humrep/dem262
  35. Koks CA, Groothuis PG, Dunselman GA, de Goeij AF and Evers JL (2000) Adhesion of menstrual endometrium to extracellular matrix: the possible role of integrin alpha(6)beta(1) and laminin interaction. Mol Hum Reprod 6, 170-177 https://doi.org/10.1093/molehr/6.2.170
  36. Puy LA, Pang C and Librach CL (2002) Immunohistochemical analysis of alphavbeta5 and alphavbeta6 integrins in the endometrium and endometriosis. Int J Gynecol Pathol 21, 167-177 https://doi.org/10.1097/00004347-200204000-00010
  37. Khoufache K, Bazin S, Girard K et al (2012) Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo. PLoS One 7, e37264 https://doi.org/10.1371/journal.pone.0037264
  38. Chen J, Gu L, Ni J, Hu P, Hu K and Shi YL (2015) MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells. Biomed Res Int 2015, 340218
  39. Rai V, Hopkisson J, Kennedy S, Bergqvist A, Barlow DH and Mardon HJ (1996) Integrins alpha 3 and alpha 6 are differentially expressed in endometrium and endometriosis. J Pathol 180, 181-187 https://doi.org/10.1002/(SICI)1096-9896(199610)180:2<181::AID-PATH620>3.0.CO;2-I
  40. Singh H and Aplin JD (2009) Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation. J Anat 215, 3-13 https://doi.org/10.1111/j.1469-7580.2008.01034.x
  41. Witz CA (2003) Cell adhesion molecules and endometriosis. Semin Reprod Med 21, 173-182 https://doi.org/10.1055/s-2003-41324
  42. Silginer M, Burghardt I, Gramatzki D et al (2016) The aryl hydrocarbon receptor links integrin signaling to the TGF-beta pathway. Oncogene 35, 3260-3271 https://doi.org/10.1038/onc.2015.387
  43. Gutierrez J, Droppelmann CA, Contreras O, Takahashi C and Brandan E (2015) RECK-Mediated beta1-Integrin Regulation by TGF-beta1 Is Critical for Wound Contraction in Mice. PLoS One 10, e0135005 https://doi.org/10.1371/journal.pone.0135005
  44. Hong SK, Park JR, Kwon OS, Kim KT, Bae GY and Cha HJ (2016) Induction of integrin beta3 by sustained ERK activity promotes the invasiveness of TGFbeta-induced mesenchymal tumor cells. Cancer Lett 376, 339-346 https://doi.org/10.1016/j.canlet.2016.04.012
  45. Yang X, Pursell B, Lu S, Chang TK and Mercurio AM (2009) Regulation of beta 4-integrin expression by epigenetic modifications in the mammary gland and during the epithelial-to-mesenchymal transition. J Cell Sci 122, 2473-2480 https://doi.org/10.1242/jcs.049148
  46. Scardigli R, Soddu S, Falcioni R, Crescenzi M, Cimino L and Sacchi A (1996) The beta 4 integrin subunit is expressed in mouse fibroblasts and modulated by transforming growth factor-beta 1. Exp Cell Res 227, 223-229 https://doi.org/10.1006/excr.1996.0271

피인용 문헌

  1. Adhesion in Physiological, Benign and Malignant Proliferative States of the Endometrium: Microenvironment and the Clinical Big Picture vol.7, pp.5, 2018, https://doi.org/10.3390/cells7050043
  2. Metabolism as an early predictor of DPSCs aging vol.9, pp.1, 2019, https://doi.org/10.1038/s41598-018-37489-4
  3. TGFβ1-induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer vol.99, pp.6, 2019, https://doi.org/10.1111/iep.12300