Effects of down-regulation of microRNA-23a on TNF-α-induced endothelial cell apoptosis through caspase-dependent pathways.
OBJECTIVE
Endothelial cell injury induced by inflammatory factors plays a critical role in the pathogenesis of numerous vascular diseases. MicroRNAs are well known to be implicated in cell proliferation and apoptosis in inflammatory responses; however, it remains to be determined whether microRNAs are associated with tumour necrosis factor (TNF)-α-mediated endothelial cell injury. The aim of the present study was to investigate the role of microRNAs in TNF-α-induced endothelial cell apoptosis.


RESULTS
Microarrays were used to analyse the global expression of microRNAs in TNF-α-stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT-PCR. After TNF-α treatment, 12 miRNAs were dramatically up-regulated and nine were down-regulated. LNA-anti-miR-23a and pre-miR-23a were found to modulate one of the markedly down-regulated miRNAs, miR-23a, which could in turn increase or attenuate TNF-α-induced endothelial cell apoptosis. Bioinformatics analysis suggested that caspase-7 and serine/threonine kinase 4 are potential targets of miR-23a. LNA-anti-miR-23a enhanced but pre-miR-23a inhibited the activation of caspase-7, serine/threonine kinase 4, and its related signalling caspase-3 after TNF-α treatment; however, neither pre-miR-23a nor LNA-anti-miR-23a had an effect on TNF-α-induced Bcl-2 activation.


CONCLUSIONS
Our results suggest that miR-23a may be involved in TNF-α-induced endothelial cell apoptosis through regulation of the caspase-7 and serine/threonine kinase 4-caspase-3 pathways.
Department of Anesthesiology, Second XiangYa Hospital, Central South University, Renmin Road no. 86, Changsha, Hunan 410011, PR China.
Wei
W
Ruan
Jun-mei
JM
Xu
Suo-bei
SB
Li
Ling-qing
LQ
Yuan
Ru-ping
RP
Dai
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology; D053179:Caspase 7 / Q000502:physiology; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D046228:Microarray Analysis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases