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Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways.
J Clin Endocrinol Metab 2010; 95(12):E403-12JC

Abstract

CONTEXT

An active angiogenesis is required for ectopic endometrial tissue growth. Our previous studies led to the identification of macrophage migration inhibitory factor (MIF), which is markedly elevated in active, vascularized, and early-stage endometriotic lesions, as a potent mitogenic factor for endothelial cells.

OBJECTIVE

Our objective was to study the mechanisms by which MIF may stimulate angiogenesis in ectopic endometrial implantation sites.

DESIGN

Primary cultures of ectopic endometrial cells were exposed to MIF, and the release of major angiogenic factors with targeted disruption of MIF signaling pathways was assessed.

PATIENTS

Patients were women found to have endometriosis during laparoscopy.

SETTING

The study was conducted at a hospital and reproduction research laboratory.

INTERVENTIONS

Biopsies were removed from endometriotic lesions.

MAIN OUTCOME MEASURES

Vascular endothelial cell growth factor (VEGF), IL-8, and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels and expression and small interfering RNA silencing of MIF CD74/CD44 receptor complex and phosphorylation of ERK and p38 MAPKs were evaluated.

RESULTS

MIF markedly up-regulated VEGF, IL-8, and MCP-1 expression in endometriotic cells. Such an effect was abolished by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a specific inhibitor of MIF, and significantly down-regulated after specific small interfering RNA silencing of CD44 or CD74. MIF treatment strongly activated ERK and p38 MAPKs, and specific inhibitors of both pathways completely blocked basal and MIF-induced VEGF, IL-8, and MCP-1 synthesis.

CONCLUSIONS

These results show for the first time that MIF exerts a potent indirect angiogenic effect by interacting with ectopic endometrial cells and inducing the secretion of major angiogenic factors via CD44, CD74, and MAPK signaling pathways and provide evidence for a possible new mechanism underlying endometriosis development and pathophysiology.

Authors+Show Affiliations

Centre de recherche, Hôpital Saint-François d'Assise, and Faculty de Médecine, Université Laval, 10, rue de l'Espinay, Local D0-711, Québec (Québec), Canada G1L 3L5.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20829186

Citation

Veillat, Véronique, et al. "Macrophage Migration Inhibitory Factor Elicits an Angiogenic Phenotype in Human Ectopic Endometrial Cells and Triggers the Production of Major Angiogenic Factors Via CD44, CD74, and MAPK Signaling Pathways." The Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 12, 2010, pp. E403-12.
Veillat V, Carli C, Metz CN, et al. Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways. J Clin Endocrinol Metab. 2010;95(12):E403-12.
Veillat, V., Carli, C., Metz, C. N., Al-Abed, Y., Naccache, P. H., & Akoum, A. (2010). Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways. The Journal of Clinical Endocrinology and Metabolism, 95(12), pp. E403-12. doi:10.1210/jc.2010-0417.
Veillat V, et al. Macrophage Migration Inhibitory Factor Elicits an Angiogenic Phenotype in Human Ectopic Endometrial Cells and Triggers the Production of Major Angiogenic Factors Via CD44, CD74, and MAPK Signaling Pathways. J Clin Endocrinol Metab. 2010;95(12):E403-12. PubMed PMID: 20829186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways. AU - Veillat,Véronique, AU - Carli,Cédric, AU - Metz,Christine N, AU - Al-Abed,Yousef, AU - Naccache,Paul H, AU - Akoum,Ali, Y1 - 2010/09/08/ PY - 2010/9/11/entrez PY - 2010/9/11/pubmed PY - 2011/1/15/medline SP - E403 EP - 12 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 95 IS - 12 N2 - CONTEXT: An active angiogenesis is required for ectopic endometrial tissue growth. Our previous studies led to the identification of macrophage migration inhibitory factor (MIF), which is markedly elevated in active, vascularized, and early-stage endometriotic lesions, as a potent mitogenic factor for endothelial cells. OBJECTIVE: Our objective was to study the mechanisms by which MIF may stimulate angiogenesis in ectopic endometrial implantation sites. DESIGN: Primary cultures of ectopic endometrial cells were exposed to MIF, and the release of major angiogenic factors with targeted disruption of MIF signaling pathways was assessed. PATIENTS: Patients were women found to have endometriosis during laparoscopy. SETTING: The study was conducted at a hospital and reproduction research laboratory. INTERVENTIONS: Biopsies were removed from endometriotic lesions. MAIN OUTCOME MEASURES: Vascular endothelial cell growth factor (VEGF), IL-8, and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels and expression and small interfering RNA silencing of MIF CD74/CD44 receptor complex and phosphorylation of ERK and p38 MAPKs were evaluated. RESULTS: MIF markedly up-regulated VEGF, IL-8, and MCP-1 expression in endometriotic cells. Such an effect was abolished by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a specific inhibitor of MIF, and significantly down-regulated after specific small interfering RNA silencing of CD44 or CD74. MIF treatment strongly activated ERK and p38 MAPKs, and specific inhibitors of both pathways completely blocked basal and MIF-induced VEGF, IL-8, and MCP-1 synthesis. CONCLUSIONS: These results show for the first time that MIF exerts a potent indirect angiogenic effect by interacting with ectopic endometrial cells and inducing the secretion of major angiogenic factors via CD44, CD74, and MAPK signaling pathways and provide evidence for a possible new mechanism underlying endometriosis development and pathophysiology. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/20829186/Macrophage_migration_inhibitory_factor_elicits_an_angiogenic_phenotype_in_human_ectopic_endometrial_cells_and_triggers_the_production_of_major_angiogenic_factors_via_CD44_CD74_and_MAPK_signaling_pathways_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2010-0417 DB - PRIME DP - Unbound Medicine ER -