Activin A induces tumorigenesis of leiomyoma via regulation of p38β MAPK-mediated signal cascade.

OBJECTIVE:The objective of this study was to investigate the role of p38-C/EBPβ signaling in leiomyoma cells and myometrial cells challenged with Activin A, and to identify specifically the isoform of p38 MAPK that mediates the effects of Activin A. METHODS:The immortalization human leiomyoma cells (HuLM) and human myometrial cells (HM), and mouse myometrial tissues were treated with Activin A (4 nM) in response to p38α/β inhibition (10 μM SB202190) or depletion (p38 α/β-targeting siRNA or p38β muscle specific-knock out mice). p38 MAPK signaling molecules (p-p38 and p-C/EBPβ) and ECM components (COL1A1 and/or FN) were analyzed by Western blotting. RESULTS:Activin A induced ECM accumulation in leiomyoma cells and myofibroblastic transformation in myometrical cells specifically by p38β MAPK. CONCLUSION:This study is the first to demonstrate that activation of C/EBPβ by p38β MAPK may contribute to tumorigenesis and progression of Activin A-induced leiomyoma. Specific p38β inhibition may represent a novel and promising intervention for leiomyoma.

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