SIGNAL TRANSDUCTION IN THE DEVELOPMENT OF ENDOMETRIOSIS

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: THE UNIVERSITY OF TOKYO
• Principal Investigator: OSUGA Yutakta The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80260496)
• Project Period (FY): 2004 – 2005
• Keywords: endometriosis / interleukin / mitogen-activated protein kinase / proliferation / protease-activated receptor 2 / 好中球

Research Abstract

BACKGROUND : Inflammation has been proposed to play essential roles in the pathophysiology of endometriosis, in which neutrophils and mast cells have been suggested to be involved. We studied whether the protease-activated receptor 2 (PAR2), which is activated by enzymes from neutrophils and mast cells, in endometriotic stromal cells (ESC) has any implication in the development of the disease. METHODS : Cultured ESC were stimulated with various concentrations of a specific PAR2 agonist peptide. Proliferating activity of the cells was determined using immunostaining of proliferating cell nuclear antigen (a cell proliferation marker), 5-bromo-2'-deoxyuridine incorporation} into DNA and cell count. The concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme-linked immunosorbent assay kits. The phosphorylation of three mitogen-activated protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis. RESULTS : Activation of PAR2 stimulated the proliferation of ESC and the secretion of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2 stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS : The activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis by inducing the growth and inflammation of endometriotic lesions.

Research Products

• [Journal Article] Mechanical stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells. (2006)
  • Author(s): Harada M., Osuga Y., Takemura Y., Yoshino O., Koga K., Hirota Y., Hirata T., Morimoto C., Yano T., Taketani Y.
  • Journal Title: Am J Physiol Endocrinol Metab 290 Pages: E268-E272
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanical, stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells. (2006)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: Am J Physiol Endocrinol Metad 290 Pages: E268-E272
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis (2005)
  • Author(s): Takemura Y., Osuga Y., Harada M., Hirata T., Koga K., Yoshino O., Hirota Y., Morimoto C., Yano T., Taketani Y.
  • Journal Title: Am J Reprod Immunol 54 Pages: 217-221
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Serum adiponectin concentrations are decreased in women with endometriosis (2005)
  • Author(s): Takemura Y., Osuga Y., Harada M., Hirata T., Koga K., Morimoto C., Hirota Y., Yoshino O., Yano T., Taketani Y
  • Journal Title: Hum Reprod 20 Pages: 3510-3513
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis. (2005)
  • Author(s): Morimoto C., Osuga Y., Yano T., Takemura Y., Harada M., Hirata T., Hirota Y., Yoshino O., Koga K., Kugu K., Taketani Y
  • Journal Title: Hum Reprod 20 Pages: 3212-3218
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Possible involvement of thrombin/protease-activated receptor 1 system in the pathogenesis of endometriosis (2005)
  • Author(s): Hirota Y., Osuga Y., Hirata T., Yoshino O., Koga K., Harada M., Morimoto C., Nose E., et al.
  • Journal Title: J Clin Endocrinol Metab 90 Pages: 3673-3679
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. (2005)
  • Author(s): Hirota Y., Osuga Y., Hirata T., Harada M., Morimoto C., Yoshino O., Koga K., Yano T., Tsutsumi O., Taketani Y
  • Journal Title: Hum Reprod 20 Pages: 3547-3553
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Concentration of adiponectin in peritoneal. (2005)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: Am J Physiol Immunol 54 Pages: 217-221
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Serum adiponectin concentrations (2005)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: Hum Reprtod 20 Pages: 3510-3513
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis. (2005)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: Hum Reprtod 20 Pages: 3212-3218
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Possible involvement of thrombin/protease-activated receptor I system in the pathogenesis of Endometriosis. (2005)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: J Clin Endocrinol Metab 90 Pages: 3673-3679
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. (2005)
  • Author(s): Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirata T, Morimura C, Yano T, Yano T, Taketani Y.
  • Journal Title: Hun Reprod 20 Pages: 3547-3553
  • Description: 「研究成果報告書概要(欧文)」より