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The macrophage stimulating protein/RON system: a potential novel target for prevention and treatment of endometriosis
S Matsuzaki1, M Canis, J L Pouly
1Department of Gynecology, Polyclinique de l'Hôtel-Dieu, CHU, Clermont-Ferrand, France.
Abstract:
Our recent DNA microarray analysis using tissue obtained by laser capture microdissection (LCM) identified up-regulation of RON (a tyrosine kinase receptor) during the late secretory phase in eutopic endometrial epithelial cells from patients with deep endometriosis compared with control endometrium from women with macroscopically normal pelvic cavities. In the present study, we further investigated mRNA expression of RON and its ligand, macrophage stimulating protein (MSP), in deep endometriotic lesions, eutopic endometrium from patients with deep endometriosis and control endometrium by using LCM and quantitative real-time RT-PCR. MSP mRNA expression in endometrial epithelial cells was significantly up-regulated in endometriosis patients during the late secretory phase compared with expression in controls. Furthermore, we detected up-regulation of MSP mRNA in ectopic endometrial epithelial cells compared with matched eutopic endometrial epithelial cells within the same patients regardless of the menstrual phase. MSP has an intrinsically dual functional nature through its receptor RON-it is a trophic cytokine preventing apoptosis and a scatter factor promoting invasion, both of which may be necessary for the initial development and growth of endometriosis. The present findings suggest that the MSP/RON system may be involved in the pathophysiology of endometriosis.
Insights
Macrophage stimulating protein (MSP) and its receptor RON are elevated in endometriosis. This MSP/RON system may drive endometriosis development by preventing cell death and promoting invasion.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Endocrinology
Background:
- Endometriosis is a complex gynecological condition.
- The molecular mechanisms underlying endometriosis pathophysiology require further elucidation.
- Previous studies identified up-regulation of RON in eutopic endometrium of endometriosis patients.
Purpose of the Study:
- To investigate the mRNA expression of macrophage stimulating protein (MSP) and its receptor RON in endometriosis.
- To compare MSP and RON expression in deep endometriotic lesions, eutopic endometrium, and control endometrium.
- To explore the role of the MSP/RON system in endometriosis development and progression.
Main Methods:
- Laser capture microdissection (LCM) for precise tissue sampling.
- Quantitative real-time RT-PCR for mRNA expression analysis.
- Comparison of gene expression across deep endometriotic lesions, eutopic endometrium from patients, and control endometrium.
Main Results:
- MSP mRNA expression was significantly up-regulated in endometrial epithelial cells of endometriosis patients during the late secretory phase compared to controls.
- MSP mRNA was also up-regulated in ectopic endometrial epithelial cells compared to matched eutopic endometrial cells within the same patients.
- RON mRNA expression was previously identified as up-regulated in eutopic endometrium during the late secretory phase.
Conclusions:
- The MSP/RON system, involving MSP as a trophic cytokine and scatter factor, may play a crucial role in endometriosis.
- MSP/RON signaling could contribute to endometriosis by preventing apoptosis and promoting cellular invasion.
- Targeting the MSP/RON pathway presents a potential therapeutic strategy for endometriosis.