BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal stem cellsopen access
- Authors
- Lee, Hyun Jik; Jung, Young Hyun; Choi, Gee Euhn; Ko, So Hee; Lee, Sei-Jung; Lee, Sang Hun; Han, Ho Jae
- Issue Date
- Oct-2017
- Publisher
- Elsevier BV
- Keywords
- Hypoxia; Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3); Mitophagy; Fatty acid synthase (FASN); Mesenchymal stem cell
- Citation
- Redox Biology, v.13, pp 426 - 443
- Pages
- 18
- Journal Title
- Redox Biology
- Volume
- 13
- Start Page
- 426
- End Page
- 443
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7173
- DOI
- 10.1016/j.redox.2017.07.004
- ISSN
- 2213-2317
- Abstract
- Mitophagy under hypoxia is an important factor for maintaining and regulating stem cell functions. We previously demonstrated that fatty acid synthase (FASN) induced by hypoxia is a critical lipid metabolic factor determining the therapeutic efficacy of umbilical cord blood-derived human mesenchymal stem cells (UCB-hMSCs). Therefore, we investigated the mechanism of a major mitophagy regulator controlling lipid metabolism and therapeutic potential of UCB-hMSCs. This study revealed that Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)-dependent mitophagy is important for reducing mitochondrial reactive oxygen species accumulation, anti-apoptosis, and migration under hypoxia. And, BNIP3 expression was regulated by CREB binding protein-mediated transcriptional actions of HIF-1 alpha and FOXO3. Silencing of BNIP3 suppressed free fatty acid (FFA) synthesis regulated by SREBP1/FASN pathway, which is involved in UCB-hMSC apoptosis via caspases cleavage and migration via cofilin-l-mediated F-actin reorganization in hypoxia. Moreover, reduced mouse skin wound-healing capacity of UCB-hMSC with hypoxia pretreatment by BNIP3 silencing was recovered by palmitic acid. Collectively, our findings suggest that BNIP3-mediated mitophagy under hypoxia leads to FASN-induced FFA synthesis, which is critical for therapeutic potential of UCB-hMSCs with hypoxia pretreatment.
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Collections - College of Medicine > Department of Biochemistry > 1. Journal Articles
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