Activin A induces leiomyoma cell proliferation, extracellular matrix (ECM) accumulation and myofibroblastic transformation of myometrial cells via p38 MAPK.

OBJECTIVE

The objective of this study was to evaluate the role of Activin A and p38β MAPK-activated signaling in human leiomyoma cells, myometrial cells and mouse myometrial tissues.

METHODS

The immortalization human leiomyoma cells (HuLM), the immortalized human myometrial cells (HM) and mouse myometrial tissues were treated with Activin A (4 nM) and/or specific p38 inhibitor SB202190 (10 μM) for different days of interval (to measure proliferation rate) or 1 h (to measure signaling molecules) or 48 h (to measure proliferating markers Ki-67, ECM mRNA, and/or ECM protein expression) by real-time PCR, Western blot, and/or immunocytochemistry.

RESULTS

Activin A induced cell proliferation and ECM proteins accumulation in HuLM cells via p38 MAPK. Activin A also induced myofibroblastic transformation in HM cells and mouse myometrical tissues via the phosphorylation of p38. The effects of Activin A in leiomyoma cells, myometrical cells and tissues were abolished by p38α/β MAPK inhibitor SB202190.

CONCLUSION

This study demonstrates Activin A-p38 MAPK signaling pathway in leiomyoma and myometrium may contribute to excessive ECM production, leiomyoma growth and progression. Targeting Activin A-p38 MAPK signaling pathway could be a potential therapeutic intervention for uterine leiomyoma.