Journal
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
Volume 64, Issue 3, Pages 209-216Publisher
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION
DOI: 10.3164/jcbn.18-112
Keywords
mesenchymal stem cells; transcriptome; hypoxia; iron chelator; autophagy
Categories
Funding
- Project Promoting The Research and Development (R&D) Center on Regenerative Medicine in Yamaguchi Prefecture
- Japan Society for the Promotion of Science [18K15815, 24659369]
- Grants-in-Aid for Scientific Research [18K15815, 24659369] Funding Source: KAKEN
Ask authors/readers for more resources
Differences in the culturing conditions of mesenchymal stem cells used in regenerative medicine may affect their differentiation ability, genome instability, and therapeutic effects. In particular, bone marrow-derived mesenchymal stem cells cultured under hypoxia are known to proliferate while maintaining an undifferentiated state and the use of deferoxamine, a hypoxia mimetic reagent, has proven to be a suitable strategy to maintain the cells under hypoxic metabolic state. Here, the deferoxamine effects were investigated in mesenchymal stem cells to gain insights into the mechanisms regulating stem cell survival. A 12-h deferoxamine treatment reduced proliferation, oxygen consumption, mitochondrial activity, and ATP production. Microarray analysis revealed that deferoxamine enhanced the transcription of genes involved in glycolysis and the HIF1 alpha pathway. Among the earliest changes, transcriptional variations were observed in HIF1 alpha, NUPR1, and EGLN, in line with previous reports showing that short deferoxamine treatments induce substantial changes in mesenchymal stem cells glycolysis pathway. NUPR1, which is induced by stress and involved in autophagy-mediated survival, was upregulated by deferoxamine in a concentration-dependent manner. Consistently, NUPR1 knockdown was found to reduce cell proliferation and increase the proapoptotic effect of staurosporine, suggesting that deferoxamine-induced NUPR1 promotes mesenchymal stem cell survival and cytoprotective autophagy. Our findings may substantially contribute to improve the effectiveness of mesenchymal stem cell-based regenerative medicine.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available