title: Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells.
abstract: Heme oxygenase 1 (HO-1) is a stress-inducible enzyme that degrades redox-active heme-producing biliverdin, carbon monoxide, and Fe(2+). 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.
authors: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors: Kati H
authors: KH
authors: Pulkkinen
authors: Seppo
authors: S
authors: Ylä-Herttuala
authors: Anna-Liisa
authors: AL
authors: Levonen
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1