title: Heme oxygenase-1 regulates postnatal lung repair after hyperoxia: role of β-catenin/hnRNPK signaling.
abstract: In the newborn, alveolarization continues postnatally and can be disrupted by hyperoxia, leading to long-lasting consequences on lung function. We wanted to better understand the role of heme oxygenase (HO)-1, the inducible form of the rate-limiting enzyme in heme degradation, in neonatal hyperoxic lung injury and repair. Although it was not observed after 3 days of hyperoxia alone, when exposed to hyperoxia and allowed to recover in air (O2/air recovered), neonatal HO-1 knockout (KO) mice had enlarged alveolar spaces and increased lung apoptosis as well as decreased lung protein translation and dysregulated gene expression in the recovery phase of the injury. Associated with these changes, KO had sustained low levels of active β-catenin and lesser lung nuclear heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein levels, whereas lung nuclear hnRNPK was increased in transgenic mice over-expressing nuclear HO-1. Disruption of HO-1 may enhance hnRNPK-mediated inhibition of protein translation and subsequently impair the β-catenin/hnRNPK regulated gene expression required for coordinated lung repair and regeneration.
authors.affiliation: Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Chhanda
authors.initials: C
authors.lastname: Biswasa
authors.forename: Qing Sara
authors.initials: QS
authors.lastname: Lin
authors.forename: Ping
authors.initials: P
authors.lastname: La
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Namba
authors.forename: Tiangang
authors.initials: T
authors.lastname: Zhuang
authors.forename: Manasa
authors.initials: M
authors.lastname: Muthu
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology*; D055370:Lung Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012261:Ribonucleoproteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C577277:HNRNPK protein, mouse; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D008565:Membrane Proteins; D012261:Ribonucleoproteins; D051176:beta Catenin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Cell proliferation; DNA damage and repair; HO-1, heme oxygenase-1; Heme oxygenase-1; KO, knockout; MEF, mouse embryonic fibroblasts; Neonatal hyperoxic lung injury and repair; O2/air, exposed to 95% oxygen for 3 days then recovered in air; OGG1, 8-oxoguanine DNA glycosylase; RAC, radial alveolar counts; SP-B, surfactant protein B; SP-C, surfactant protein C; hnRNPK, heterogeneous nuclear ribonucleoprotein protein K; β-catenin/hnRNPK
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