Publication: Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts
Issued Date
2014-01-01
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ISSN
10974644
07302312
07302312
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2-s2.0-84892912997
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Cellular Biochemistry. Vol.115, No.4 (2014), 785-793
Suggested Citation
Keith Dadson, Helen Chasiotis, Sivaporn Wannaiampikul, Rungsunn Tungtrongchitr, Aimin Xu, Gary Sweeney Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts. Journal of Cellular Biochemistry. Vol.115, No.4 (2014), 785-793. doi:10.1002/jcb.24722 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/33399
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Title
Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts
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Abstract
Defects in adiponectin action have been implicated in the development of cardiac dysfunction in obesity and diabetes. Cardiac fibroblasts play an important role in regulating extracellular matrix remodeling yet little is known regarding the direct effects of adiponectin on cardiac fibroblasts. In this study, we first demonstrated temporal relocalization of cellular APPL1 in response to adiponectin in primary cardiac fibroblasts and that siRNA-mediated knockdown of APPL1 attenuated stimulation of AMPK by adiponectin. The cell surface content of MT1-MMP and activation of MMP2 were induced by adiponectin and these responses were dependent on AMPK signaling. Enhanced MMP activity facilitated increased fibroblast migration in response to adiponectin which was also prevented by inhibition of AMPK, with no change in cell proliferation observed. Collagen and elastin immunofluorescence demonstrated reorganization of the extracellular matrix in accordance with increased MMP activity, whereas quantitative mRNA analysis, 3H-proline incorporation and picrosirius red assays showed no change in intracellular or extracellular total collagen levels in response to adiponectin. In summary, these data are the first to report the adiponectin stimulated APPL1-AMPK signaling axis in cardiac fibroblasts and characterize MT1-MMP translocation, MMP2 activity and cell migration as functional outcomes. These effects may be of significance in heart failure associated with obesity and diabetes. J. Cell. Biochem. 115: 785-793, 2014. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.