Genetic ablation of Bach1 gene enhances recovery from hyperoxic lung injury in newborn mice via transient upregulation of inflammatory genes

Ito, Masato; Nagano, Nobuhiko; Arai, Yasumasa; Ogawa, Ryo; Kobayashi, Shingo; Motojima, Yukiko; Go, Hayato; Tamura, Masanori; Igarashi, Kazuhiko; Dennery, Phyllis A.; Namba, Fumihiko

doi:10.1038/pr.2017.17

Cited by 17 publications

(21 citation statements)

References 35 publications

(39 reference statements)

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“…While Nrf2 induces the expression of HO-1, Bach1, a leucin zipper protein, is a physiological repressor of HO-1 [95]. The effects of silencing Bach1 in a mouse model of hyperoxic lung injury has been recently studied [96,97]. Go et al [97] demonstrated that under physiological conditions, miR-196a is able to silence Bach1 giving rise to an increase in lung HO-1 expression, whereas under hyperoxic stress miR-196a is degraded with a consequent reduction in HO-1 levels.…”

Section: Nrf2 and Heme Oxygenase-1 (Ho-1) Main Characters Of The Samementioning

confidence: 99%

“…Go et al [97] demonstrated that under physiological conditions, miR-196a is able to silence Bach1 giving rise to an increase in lung HO-1 expression, whereas under hyperoxic stress miR-196a is degraded with a consequent reduction in HO-1 levels. Ito et al [96] developed a mouse model of Bach1 −/− which demonstrated improved alveolarization after 4 days neonatal hyperoxic exposure (21 or 95% oxygen) and room air recovery. After assessing lung histology and measuring mRNA levels of lung Bach1, HO-1, interleukin (IL)-6 (IL-6), and monocyte chemoattractant protein (MCP)-1 it was observed a significant increment in HO-1, IL-6, and (MCP)-1 mRNA levels.…”

Section: Nrf2 and Heme Oxygenase-1 (Ho-1) Main Characters Of The Samementioning

confidence: 99%

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Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries

et al. 2017

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Bronchopulmonary dysplasia (BPD) is a chronic illness that usually originates in preterm newborns. Generally, BPD is a consequence of respiratory distress syndrome (RDS) which, in turn, comes from the early arrest of lung development and the lack of pulmonary surfactant. The need of oxygen therapy to overcome premature newborns' compromised respiratory function generates an increasing amount of reactive oxygen species (ROS), the onset of sustained oxidative stress (OS) status, and inflammation in the pulmonary alveoli deputies to respiratory exchanges. BPD is a severe and potentially life-threatening disorder that in the most serious cases, can open the way to neurodevelopmental delay. More importantly, there is no adequate intervention to hamper or treat BPD. This perspective article seeks to review the most recent and relevant literature describing the very early stages of BPD and hyperoxic lung injuries focussing on nuclear factor erythroid derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. Indeed, Nrf2/HO1 activation in response to OS induced lung injury in preterm concurs to the induction of certain number of antioxidant, anti-inflammatory, and detoxification pathways that seem to be more powerful than the activation of one single antioxidant gene. These elicited protective effects are able to counteract/mitigate all multifaceted aspects of the disease and may support novel approaches for the management of BPD.

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Section: Nrf2 and Heme Oxygenase-1 (Ho-1) Main Characters Of The Samementioning

confidence: 99%

Section: Nrf2 and Heme Oxygenase-1 (Ho-1) Main Characters Of The Samementioning

confidence: 99%

Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries

et al. 2017

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“…We hypothesized that BACH1 might regulate ferroptosis by inhibiting the expression of these genes. In addition, since BACH1 is involved in the exacerbation of various diseases involving oxidative stress, such as ischemic heart disease (Yano et al, 2006), hyperoxic lung injury (Ito et al, 2017), trinitrobenzene sulfonic acid-induced colitis (Harusato et al, 2013), nonalcoholic steatohepatitis (Inoue et al, 2011), and spinal cord injury (Kanno et al, 2009), BACH1 may exacerbate the severity of these diseases through ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis is programmed by the coordinated regulation of glutathione and iron metabolism by BACH1

Nishizawa

Matsumoto

Shindo

et al. 2019

Preprint

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1Ferroptosis is an iron-dependent programmed cell death resulting from alterations of 2 metabolic processes. However, its regulation and physiological significance remain to be 3 elucidated. By analyzing transcriptional responses of murine embryonic fibroblasts 4 exposed to the ferroptosis-inducer erastin, we found that a set of genes related to oxidative 5 stress protection was induced upon ferroptosis. We further showed that the transcription 6 factor BACH1 promoted ferroptosis by repressing the expression of a subset of 7 erastin-inducible genes involved in the synthesis of glutathione or metabolism of 8 intracellular labile iron, including Gclm, Gclc, Slc7a11, Hmox1, Fth1, Ftl1, and Slc40a1. 9 Compared with wild-type mice, Bach1 -/mice showed resistance to myocardial infarction, 10

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“…Exposure to oxidative stresses results in the dissociation of Keap1 from Nrf2, therefore Nrf2 translocate to the nucleus and binds to the ARE sequence of several cytoprotective genes to induce transcription, including HO‐1 gene . BTB and CNC homology 1 (Bach1) is a transcriptional repressor of HO‐1, and the antioxidant effect of HO‐1 is enhanced in Bach1 deficiency mice . In addition, it is reported that Bach1 can competitively bind to ARE‐like enhancer of HO‐1 to antagonize Nrf2 binding in cells unexposed to oxidative damage …”

Section: Introductionmentioning

confidence: 99%

“…17 BTB and CNC homology 1 (Bach1) is a transcriptional repressor of HO-1, 18,19 and the antioxidant effect of HO-1 is enhanced in Bach1 deficiency mice. 20,21 In addition, it is reported that Bach1 can competitively bind to ARE-like enhancer of HO-1 to antagonize Nrf2 binding in cells unexposed to oxidative damage. 22 In the present article, we explored the roles of HO-1 pathway and the regulatory mechanisms of this pathway using HO-1 inducer cobalt protoporphyrin (Copp) and HO-1 inhibitor zinc protoporphyrin (Znpp) in lung injury following LIR in rats.…”

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confidence: 99%

Protective effects of HO‐1 pathway on lung injury subsequent to limb ischemia reperfusion

Liu

et al. 2019

The Kaohsiung J of Med Scie

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Limb ischemia reperfusion (LIR) can activate endogenous cytoprotective mechanisms by generating specific proteins against reperfusion injury in remote organs. The present study investigated the roles of heme oxygenase‐1 (HO‐1) pathway and the molecular mechanisms underlying the regulation of this pathway on lung injury following LIR. LIR was induced by ischemia for 4 hours followed by reperfusion for 6 hours (LIR 6 hours) or 16 hours (LIR 16 hours) in male Sprague‐Dawley rats. HO‐1 inducer cobalt protoporphyrin (Copp) or HO‐1 inhibitor zinc protoporphyrin (Znpp) was intravenously injected 24 hours before ischemia. The animals were randomly divided into nine groups, including normal control, LIR 6 hours, LIR 16 hours, Copp, Copp + LIR 6 hours, Copp + LIR 16 hours, and Znpp, Znpp+ LIR 6 hours, and Znpp + LIR 16 hours groups (each group included four samples). Lung injury was examined through histopathology. Quantitative real‐time PCR, immunohistochemistry and Western blot were applied to detect the mRNA and protein levels of HO‐1, Nrf2, and Bach1. Our study showed that LIR induced Nrf2 upregulation but Bach1 downregulation to promote HO‐1 expression in lung tissues. Activation of HO‐1 pathway by Copp potentially enhanced Nrf2 expression but inhibition of the pathway by Znpp promoted Bach1 expression. Inducer of HO‐1 pathway, Copp injection improved the lung injury. Nevertheless, Znpp injection aggravated the lung injury following LIR. Our findings suggested that activated HO‐1 pathway might exert protective effects on the lung injury following LIR.

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Genetic ablation of Bach1 gene enhances recovery from hyperoxic lung injury in newborn mice via transient upregulation of inflammatory genes

Abstract: Bach1 newborn mice were well-recovered from hyperoxia-induced lung injury. This effect is likely achieved by the antioxidant/anti-inflammatory activity of HO-1 or by the transient overexpression of proinflammatory cytokines.

Cited by 17 publications

References 35 publications

Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries

Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries

Ferroptosis is programmed by the coordinated regulation of glutathione and iron metabolism by BACH1

Protective effects of HO‐1 pathway on lung injury subsequent to limb ischemia reperfusion

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