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Overexpression of fibroblast growth factor‐21 (FGF‐21) protects mesenchymal stem cells against caspase‐dependent apoptosis induced by oxidative stress and inflammation
Author(s) -
Linares Gabriel R.,
Leng Yan,
Maric Dragan,
Chuang DeMaw
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11409
Subject(s) - staurosporine , mesenchymal stem cell , microbiology and biotechnology , fibroblast growth factor , apoptosis , neuroprotection , biology , oxidative stress , stem cell , cancer research , immunology , signal transduction , pharmacology , endocrinology , biochemistry , receptor , protein kinase c
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 (H 2 O 2 ), 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 H 2 O 2 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.