Abstract | AIMS: To establish a functional link between microRNA-107 (miR-107) and stem cell survival during ischemic preconditioning (IPC) of stem cells with multiple cycles of brief anoxia/re-oxygenation (10 or 30 min, one to three cycles) and show that the cytoprotective effects were independent of hypoxamir-210. RESULTS: We demonstrated the induction of miR-107 in response to the IPC-induced activation of Akt/ hypoxia inducible factor-1α (HIF-1α) in preconditioned mesenchymal stem cells ((PC)MSC), which showed improved survival during subsequent exposure to 6 h of lethal anoxia (p<0.05 vs. non-preconditioned MSC[(non-PC)MSC]). In silico analysis and luciferase activity assay confirmed programmed cell death-10 (PDCD10) as a putative target of miR-107 in (PC)MSC, which was significantly reduced during IPC and inversely related to stem cell survival under 6 h of lethal anoxia. Loss-of-function studies with miR-107 antagomir showed a significantly reduced survival of (PC)MSC. A comparison of miR-107 and miR-210 showed that both miRs participated independently via their respective putative target genes Pdcd10 and Casp8ap2. The simultaneous abrogation of Pdcd10 and Casp8ap2 had a stronger effect on (PC)MSC survival under lethal anoxia. The transplantation of (PC)MSC in an acute model of myocardial infarction showed a significantly improved survival of transplanted (PC)MSC with concomitantly enhanced miR-107 expression in (PC)MSC-transplanted animal hearts. INNOVATION: Cytoprotection afforded by IPC is regulated by miR-107 induction via Pdcd10 independent of miR-210/Casp8ap2 signaling, and the simultaneous abrogation miR-107/miR-210 has a stronger effect on the loss of (PC)MSC survival. CONCLUSION: IPC enhances stem cell survival via the combined participation of hypoxia responsive miRs miR-107 and miR-210 via their respective putative target genes Pdcd10 and Casp8ap2.
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Authors | Ha Won Kim, Faryal Mallick, Shazia Durrani, Muhammad Ashraf, Shujia Jiang, Khawaja Husnain Haider |
Journal | Antioxidants & redox signaling
(Antioxid Redox Signal)
Vol. 17
Issue 8
Pg. 1053-65
(Oct 15 2012)
ISSN: 1557-7716 [Electronic] United States |
PMID | 22482882
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Apoptosis Regulatory Proteins
- CASP8AP2 protein, rat
- Carrier Proteins
- Hypoxia-Inducible Factor 1, alpha Subunit
- MIRN210 microRNA, rat
- MicroRNAs
- PDCD10 protein, rat
- RNA, Messenger
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Topics |
- Animals
- Apoptosis Regulatory Proteins
(genetics, metabolism)
- Brain Ischemia
(metabolism, pathology)
- Carrier Proteins
(genetics, metabolism)
- Cell Survival
- Cytoprotection
- Female
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- Ischemic Preconditioning
- Male
- Mesenchymal Stem Cells
(metabolism, pathology)
- MicroRNAs
(genetics, metabolism)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Inbred F344
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