RESUMO
Although stem cells from mice deficient of FGF2 have been reported to display enhanced capacity for adipogenesis, the literature using in vitro cell culture system has so far reported conflicting results on the role of FGF2 in adipogenesis. We here demonstrate that FGF2, depending on concentration, can function as either a positive or negative factor of in vitro adipogenesis by regulating activation of the ERK signaling pathway. FGF2 at concentrations lower than 2 ng/ml enhanced in vitro adipogenesis of human adipose-derived stem cells (hASCs). However, FGF2 at concentrations higher than 10 ng/ml was able to suppress adipogenesis by maintaining sustained phosphorylation of ERK and function as a dominant negative adipogenic factor toward BMP ligands. Expression levels of FGF2 in the fat tissues from high fat diet induced obese C57BL/6 mice were lower than those from normal chow diet mice, indicating that expression levels of FGF2 in the fat tissues might be in reverse correlation with the size of fat tissues. Our observation of concentration dependent biphasic effect as well as dominant negative effect of FGF2 on adipogenesis provides a mechanistic basis to understand roles of FGF2 in adipogenesis and development of fat tissues.
Assuntos
Adipogenia , Tecido Adiposo/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Obesidade/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Dieta Hiperlipídica , Modelos Animais de Doenças , Fator 2 de Crescimento de Fibroblastos/genética , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologiaRESUMO
Abnormal degradation of matrix components due to dysregulated expression of matrix metalloproteinase (MMP)-9 in macrophages has been linked to progression of acute cerebral ischemia and atherosclerosis. We report that lithium chloride (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation of glycogen synthase kinase-3beta and suppress lipopolysaccharide-mediated upregulation of MMP-9 expression in murine macrophage RAW264.7 cells in a dose-dependent manner. Suppression of MMP-9 expression by LiCl or CHIR99021 did not result after inhibition of kinases involved in NFκB or AP-1 family proteins, but from changes in the activity of histone deacetylases. Beneficial effects on atherosclerosis or cerebral ischemia in animal studies caused by LiCl may be in part explained by the suppression of MMP-9 gene expression.