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

Kati H Pulkkinen, Seppo Ylä-Herttuala, Anna-Liisa Levonen
Free Radical Biology & Medicine 2011 December 1, 51 (11): 2124-31
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"