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

作者：Bao, Huiqiong; Sin, Thomas K.; Zhang, Guohua^*

来源：Biochemical and Biophysical Research Communications, 2018, 504(2): 447-453.

DOI：10.1016/j.bbrc.2018.08.171

• Extracellular matrix
• Myofibroblastic transformation
• p38 alpha/beta MAPK
• SB202190
• Uterine leiomyoma

Objective: The objective of this study was to evaluate the role of Activin A and p38 beta 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 mu M) 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 p38 alpha/beta 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. Published by Elsevier Inc.

• 出版日期2018-10-2
• 单位广东省人民医院