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.