Effect of Regulating PPARγ by mTOR Signaling on Adipogenesis of Bone Marrow Mesenchymal Stem Cells from Aplastic Anemia

Abstract

To study the effect and mechanism of mTOR signaling on adipogenesis of bone marrow mesenchymal stem cells(BM-MSCs) from aplastic anemia (AA) patients through regulation of PPARγ. BM-MSCs were isolated from 24 newly diagnosed AA patients and 24 healthy controls. The surface antigen expression of BM-MSCs was identified by flow cytometry. The capacity of adipogenic differentiation of BM-MSCs was determined by lipid droplets based on Oil Red O staining and by the expression of FABP4 based on Western blot. Protein levels of mTOR signaling and PPARγ were tested by immunofluorescence and Western blot. AA BM-MSCs displayed an enhanced capacity of differentiating into adipocytes, compared with control BM-MSCs. It was found that mTOR was activated in AA BM-MSCs. Moreover, the expression levels of p-mTOR and PPAR-γ in AA BM-MSCs showed a parallel differentiation-dependent increase during adipogenic differentiation, which were significantly higher than that of control BM-MSCs at the same time point of adipogenic differentiation. mTOR inhibitor rapamycin did not only inhibit the adipogenic differentiation of BM-MSCs from AA pateints at the early-middle stage, but also partly reversed the adipogenic differention of BM-MSCs from AA pateints at the late stage by PPARγ regulation. mTOR signaling may play a critical role in the adipogenic differentiation of BM-MSCs from AA patients by positively regulating PPARγ expression.