Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells

作者：Pulkkinen Kati H; Yla Herttuala Seppo; Levonen Anna Liisa^*

来源：Free Radical Biology and Medicine, 2011, 51(11): 2124-2131.

DOI：10.1016/j.freeradbiomed.2011.09.014

• miR-155
• BACH1
• HMOX1
• HO-1
• Endothelial
• NF-kappa B
• Free radicals

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-kappa B in human endothelial cells, but functional NF-kappa B-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 TNF alpha-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 TNF alpha via an NF-kappa B-dependent mechanism with a subsequent increase in HMOX1 expression. We propose that increased HMOX1 expression in endothelial cells by TNF alpha results from miR-155-induced repression of BACH1 rather than direct induction of HMOX1 via NF-kappa B, and that miR-155 is cytoprotective during inflammation by elevating HO-1 expression in endothelial cells.

• 出版日期2011-12-1