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Biochem Biophys Res Commun. 2018 Oct 2;504(2):447-453. doi: 10.1016/j.bbrc.2018.08.171. Epub 2018 Sep 5.

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

Author information

1
Department of Gynecology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
2
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
3
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: guohuazhangcn@gmail.com.

Abstract

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.

KEYWORDS:

Extracellular matrix; Myofibroblastic transformation; SB202190; Uterine leiomyoma; p38α/βMAPK

PMID:
30195496
DOI:
10.1016/j.bbrc.2018.08.171
[Indexed for MEDLINE]

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