title: [Reception and signal transduction implied in the differentiation of stem cells from human bone marrow until adipocytes].
abstract: Glucagon-like peptide-1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. However the role of GLP-1 in human bone marrow-derived mesenchymal stem cells (hMSCs), if any, remains unknown. The effects of GLP-lin hMSCs were tested with regard to cell proliferation, cytoprotection, and cell differentiation into adipocytes. The signalling pathways involved in these processes were also analyzed. Cells were characterized by biochemical and morphological approaches before and after being induce to differentiate into adipocytes. PCNA protein levels were used as an protein index, whereas cell apoptosis was studied by deprivation of fetal bovine serum. Isolated hMSCs expressed stem cell markers as well as mRNA and GLP-1 receptor protein. GLP-1 increased the proliferarion of hMSCs, which decreased when they were induced to differentiate into adipocytes.This process produced biochemical and morphological changes in cells expressing PPARgamma, C/EBPbeta, AP2, and LPL in a time-dependent pattern. Notably, GLP-1 significantly reduced the expression of PPARgamma, C/EBPbeta, and LPL. These effects were exerted at least through the MEK and PKC signaling pathways. In addition, GLP-1 significantly reduced cell apoptosis. Our data indicate that, in hMSCs, GLP-1 promotes cellular proliferation and cytoprotection and prevents cell differentiation into adipocytes. These latter findings underscore the potential therapeutic role of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and, additionally, could bolster the maintenance of hMSC stores by promoting the proliferation and cytoprotection of undifferentiated hMSC. These data suggest that the GLP-1 may have some function during embryonic life. Thus, both the peptide and its receptor were identified early in the mouse development, as well as GLP-1 modified significantly gene expression in mouse undifferentiated pluripotent cells. These findings also suggest that the pathophysiological implications of GLP-1 imbalance in adulthood may have a counterpart during development.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, 28040-Madrid.
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio García
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*