Leptin increases mitochondrial OPA1 via GSK3-mediated OMA1 ubiquitination to enhance therapeutic effects of mesenchymal stem cell transplantation

Cell Death & Disease
Fan YangJian'an Wang

Abstract

Accumulating evidence revealed that mesenchymal stem cells (MSCs) confer cardioprotection against myocardial infarction (MI). However, the poor survival and engraftment rate of the transplanted cells limited their therapeutic efficacy in the heart. The enhanced leptin production associated with hypoxia preconditioning contributed to the improved MSCs survival. Mitochondrial integrity determines the cellular fate. Thus, we aimed to investigate whether leptin can enhance mitochondrial integrity of human MSCs (hMSCs) to protect against various stress. In vivo, transplantation of leptin-overexpressing hMSCs into the infarcted heart resulted in improved cell viability, leading to enhanced angiogenesis and cardiac function. In vitro, pretreatment of hMSCs with recombinant leptin (hMSCs-Leppre) displayed improved cell survival against severe ischemic condition (glucose and serum deprivation under hypoxia), which was associated with increased mitochondrial fusion. Subsequently, Optic atrophy 1 (OPA1), a mitochondrial inner membrane protein that regulates fusion and cristae structure, was significantly elevated in the hMSCs-Leppre group, and the protection of leptin was abrogated by targeting OPA1 with a selective siRNA. Furthermore, OM...Continue Reading

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Sep 30, 2018·Antioxidants & Redox Signaling·Elianne P BulthuisWerner J H Koopman
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Methods Mentioned

BETA
ubiquitination
FACS
transmission electron microscopy
co-immunoprecipitation
co-IP
GTPase
transfection
transfections
confocal microscopy
flow cytometry

Software Mentioned

Image
OROBOROS
Photoshop
Plus
Pro
Adobe Photoshop
SPSS

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