activation of protein kinase a and exchange protein directly activated by camp promotes adipocyte differentiation of human mesenchymal stem cells激活蛋白激酶和交换蛋白直接激活人类间充质干细胞的营地促进脂肪细胞的分化.pdfVIP

Activation of Protein Kinase A and Exchange Protein Directly Activated by cAMP Promotes Adipocyte Differentiation of Human Mesenchymal Stem Cells 1,2 2,3 2 4 5 Bingbing Jia , Lise Madsen , Rasmus Koefoed Petersen , Nathalie Techer , Reidun Kopperud , 2 5 ´ 4 1 4 2 Tao Ma , Stein Ove Døskeland , Gerard Ailhaud , Jinfu Wang *, Ez-Zoubir Amri , Karsten Kristiansen * 1 Institute of Cell Biology and Genetics, College of Life Sciences, Zhejiang University, Hangzhou, People’s Republic of China, 2 Department of Biology, University of ´ Copenhagen, Copenhagen, Denmark, 3 National Institute of Nutrition and Seafood Research, Bergen, Norway, 4 IBV, Universite de Nice Sophia-Antipolis, UMR7277 CNRS - ´ ´ UMR1091 INSERM, Faculte de Medecine, Nice, France, 5 Department of Biomedicine, University of Bergen, Bergen, Norway Abstract Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical