Overexpression of fibroblast growth factor-21 (FGF-21) protects mesenchymal stem cells against caspase-dependent apoptosis induced by oxidative stress and inflammation.
The clinical application of stem cells offers great promise as a potential avenue for therapeutic use in neurodegenerative diseases. However, cell loss after transplantation remains a major challenge, which currently plagues the field. On the basis of our previous findings that fibroblast growth factor 21 (FGF-21) protected neurons from glutamate excitotoxicity and that upregulation of FGF-21 in a rat model of ischemic stroke was associated with neuroprotection, we proposed that overexpression of FGF-21 protects bone marrow-derived mesenchymal stem cells (MSCs) from apoptosis. To test this hypothesis, we examined whether the detrimental effects of apoptosis can be mitigated by the transgenic overexpression of FGF-21 in MSCs. FGF-21 was transduced into MSCs by lentivirus and its overexpression was confirmed by quantitative polymerase chain reaction. Moreover, FGF-21 overexpression did not stimulate the expression of other FGF family members, suggesting it does not activate a positive feedback system. The effects of hydrogen peroxide (H2 O2 ), tumor necrosis factor-α (TNF-α), and staurosporine, known inducers of apoptosis, were evaluated in FGF-21 overexpressing MSCs and mCherry control MSCs. Caspases 3 and 7 activity was markedly and dose-dependently increased by all three stimuli in mCherry MSCs. FGF-21 overexpression robustly suppressed caspase activation induced by H2 O2 and TNF-α, but not staurosporine. Moreover, the assessment of apoptotic morphological changes confirmed the protective effects of FGF-21 overexpression. Taken together, these results provide compelling evidence that FGF-21 plays a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation and merits further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies.
['Linares|Gabriel R|GR|', 'Leng|Yan|Y|', 'Maric|Dragan|D|', 'Chuang|De-Maw|DM|']
D000818:Animals D017209:Apoptosis D002478:Cells, Cultured D005346:Fibroblast Growth Factors D006861:Hydrogen Peroxide D007249:Inflammation D059630:Mesenchymal Stem Cells D051379:Mice D008810:Mice, Inbred C57BL D018384:Oxidative Stress D019311:Staurosporine D014409:Tumor Necrosis Factor-alpha
oxidative stress hydrogen peroxide TNF-α caspase activation