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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Differential signalling through ALK-1 and ALK-5 regulates leptin expression in mesenchymal stem cells
Stem Cells and Development, Volume 21, No. 11, Year 2012
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Description
Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known about its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts (SVF). Here, we investigated leptin expression in MSC from bone marrow (BM-MSC) and umbilical cord matrix (UMSC). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Transforming growth factor β1 (TGF-β1) markedly inhibited the endogenous- and glucocorticoid-induced leptin expression in BM-MSC. Since TGF-β1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways, we analyzed the expression of proteins from both pathways. In BM-MSC, TGF-β1 increased phosphorylated Smad2 (p-Smad2) expression, while ALK-5 inhibitor (SB431542) induced leptin expression and significantly restored TGF-β1-induced leptin inhibition. In addition, both prednisolone and SB431542 increased p-Smad1/5 expression. These results suggested the ALK-5-Smad2 pathway as an inhibitor of leptin expression, while ALK-1-Smad1/5 as an activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-βRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC, and UMSC that was correlated to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin nonproducer MSC for cell therapy protocols where leptin expression is not suitable. © 2012, Mary Ann Liebert, Inc.
Authors & Co-Authors
Zeddou, Mustapha
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Morocco, Oujda
Université Mohammed Premier Oujda
Relić, Biserka
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Malaise, Olivier
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Charlier, Edith
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Desoroux, Aline
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Beguin, Yves
Belgium, Liege
Centre Hospitalier Universitaire de Liege
de Seny, Dominique
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Malaise, Michel G.
Belgium, Liege
Centre Hospitalier Universitaire de Liege
Statistics
Citations: 19
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.1089/scd.2011.0321
ISSN:
15473287
e-ISSN:
15578534
Research Areas
Cancer