Huiqiong Bao1, Thomas K Sin2, Guohua Zhang3. 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. Published by Elsevier Inc.
OBJECTIVE: The objective of this study was to evaluate the role of Activin A and p38β MAPK-activated signaling in humanleiomyoma cells, myometrial cells and mouse myometrial tissues. METHODS: The immortalization humanleiomyoma 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. Published by Elsevier Inc.
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