AIMS: 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. METHODS AND 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. CONCLUSION: 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.
AIMS: 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. METHODS AND 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. CONCLUSION: 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.
Authors: Xiang-Yang Zhu; Behzad Ebrahimi; Alfonso Eirin; John R Woollard; Hui Tang; Kyra L Jordan; Michael Ofori; Ahmed Saad; Sandra M S Herrmann; Allan B Dietz; Stephen C Textor; Amir Lerman; Lilach O Lerman Journal: J Am Soc Nephrol Date: 2014-09-30 Impact factor: 10.121