کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1908921 | 1046693 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells](/preview/png/1908921.png)
Heme oxygenase 1 (HO-1) is a stress-inducible enzyme that degrades redox-active heme-producing biliverdin, carbon monoxide, and Fe2+. It protects cells under various stress conditions and mediates anti-inflammatory and vasodilatory effects in the endothelium. The expression of HMOX1, the HO-1 gene, is highly inducible and its transcriptional regulation is complex. HMOX1 is induced by various proinflammatory stimuli via NF-κB in human endothelial cells, but functional NF-κB-binding elements have not been identified from the human gene. However, the regulation of HMOX1 by the antioxidant-response element is firmly established, with the transcription factor BACH1 serving as a repressor and Nrf2 as an enhancer. miR-155 is one of the TNFα-inducible endothelial microRNAs predicted to bind to the BACH1 mRNA. Oligonucleotides mimicking miR-155 efficiently inhibited BACH1 protein translation, resulting in a concentration-dependent increase in HMOX1 mRNA and protein expression in human umbilical vein endothelial cells. Moreover, endogenous miR-155 was upregulated by TNFα via an NF-κB-dependent mechanism with a subsequent increase in HMOX1 expression. We propose that increased HMOX1 expression in endothelial cells by TNFα results from miR-155-induced repression of BACH1 rather than direct induction of HMOX1 via NF-κB, and that miR-155 is cytoprotective during inflammation by elevating HO-1 expression in endothelial cells.
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► TNFα induces miR-155 expression via NF-κB pathway in endothelial cells.
► miR-155 represses BACH1 protein allowing cytoprotective HMOX1 expression.
► Elevated miR-155 expression is beneficial in vascular endothelial cells.
Journal: Free Radical Biology and Medicine - Volume 51, Issue 11, 1 December 2011, Pages 2124–2131