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

Biochem Biophys Res Commun. 2020 Aug 20;529(2):379-385. doi: 10.1016/j.bbrc.2020.05.079. Epub 2020 Jul 1.

Abstract

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.

Keywords: Activin A; C/EBPβ; Isoform; Uterine leiomyoma; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / metabolism*
  • Animals
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Inbred C57BL
  • Myometrium / metabolism
  • Myometrium / pathology
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • activin A
  • Activins