Molecular Network Analysis of Endometriosis Reveals a Role for c-Jun–Regulated Macrophage Activation

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Science Translational Medicine  05 Feb 2014:
Vol. 6, Issue 222, pp. 222ra16
DOI: 10.1126/scitranslmed.3007988

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Endometriosis: Embracing Complexity

Despite its widespread contribution to infertility and debilitating pelvic pain, treatments for endometriosis—an invasive displacement of endometrial tissue outside the uterus—primarily address symptoms and fall short on combating the underlying disease. Avenues for targeted intervention have been lacking, in part due to significant patient heterogeneity that hampers reproducible findings across diverse study populations. To overcome this hurdle, Beste et al. have applied a data-driven strategy to uncover the natural variation in pelvic inflammatory status across a broad cohort of endometriosis patients. By naïvely characterizing comprehensive molecular profiles for each patient, the authors were able to identify a coherent signature of macrophage activity that was otherwise obscured by conventional staging criteria. Further experiments on isolated macrophages revealed a refined signature that unexpectedly implicated the c-Jun N-terminal kinase (JNK) signaling pathway. By confirming that small-molecule inhibition of JNK signaling broadly curbed macrophage inflammatory activity, this work provides a possible lead for future experimental and clinical studies into curtailing the deleterious inflammatory response to endometriotic lesions. If this general approach is validated in larger populations, such profiles may also be helpful as a complementary tool to better identify patients at greater risk for recurrence who would benefit from aggressive treatment.