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Published on: June 3, 2018
Bone marrow mesenchymal stem cells inhibit cardiac hypertrophy by enhancing FoxO1 transcription
Jiantao Qiu1, Huaiteng Xiao2, Shunchang Zhou3
1Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Insights
Bone marrow-derived mesenchymal stem cells (BMSCs) inhibit cardiac hypertrophy by activating the 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway and downregulating forkhead box O 1 (FoxO1) signaling in cardiomyocytes.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Molecular Cardiology
Background:
- Bone marrow-derived mesenchymal stem cells (BMSCs) show promise for treating heart diseases.
- Previous research indicates stem cells can inhibit cardiac hypertrophy, but the underlying mechanisms require further investigation.
Purpose of the Study:
- To elucidate the mechanism by which BMSCs inhibit cardiomyocyte hypertrophy.
- To explore the role of the 5 -adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O 1 (FoxO1) signaling pathways.
Main Methods:
- Cardiomyocyte hypertrophy was induced using isoproterenol (ISO) in cultured rat cells.
- Messenger RNA expression was analyzed via microarray, and protein levels were assessed using Western blot.
- Pathway enrichment analysis identified key signaling pathways involved.
Main Results:
- BMSC coculture upregulated the p-AMPK/AMPK ratio and downregulated the p-FoxO1/FoxO1 ratio.
- AMPK inhibition by Compound C blocked FoxO1 downregulation, while FoxO1 antagonism reduced BMSC-mediated inhibition of hypertrophy.
- BMSCs partially inhibit cardiomyocyte hypertrophy via the AMPK-FoxO1 pathway.
Conclusions:
- BMSCs exert a protective effect against cardiomyocyte hypertrophy.
- The AMPK-FoxO1 signaling axis is a key mediator of BMSC-induced cardioprotection.
- This study provides mechanistic insights into stem cell therapy for cardiac hypertrophy.
Abstract:
Bone marrow-derived mesenchymal stem cells (BMSCs) have therapeutic potential for certain heart diseases. Previous studies have shown that stem cells inhibit cardiac hypertrophy; however, it is necessary to explore the mechanisms underlying this effect. This study aimed to investigate the possible mechanism underlying the inhibitory effect of BMSCs on cardiomyocyte hypertrophy. We induced cardiomyocyte hypertrophy in cultured rat cells through isoproterenol (ISO) treatment with or without BMSC coculture. A microarray was performed to analyze messenger RNA expression in response to ISO treatment and BMSC coculture. Pathway enrichment analysis showed that the expression of differential genes was closely related to the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and that the expression of forkhead box O 1 (FoxO1) was significantly increased in the presence of BMSCs. Furthermore, we determined the expression levels of p-AMPK/AMPK and p-FoxO1/FoxO1 by western blot analysis. The expression of p-AMPK/AMPK was upregulated, whereas that of p-FoxO1/FoxO1 was downregulated upon coculturing with BMSCs. The AMPK-specific antagonist Compound C inhibited the downregulation of p-FoxO1/FoxO1 induced by the BMSC coculture. Furthermore, treatment with the specific FoxO1 antagonist AS1842856 reduced the inhibitory effects of BMSCs on cardiomyocyte hypertrophy in vivo and in vitro. Our present study demonstrates the inhibition of cardiomyocyte hypertrophy by BMSCs, which occurs partly through the AMPK-FoxO1 signaling pathway.
