Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung.
Developmentally important genes have recently been linked to tissue regeneration and epithelial cell repair in neonatal and adult animals in several organs, including liver, skin, prostate, and musculature. We hypothesized that developmentally important genes play roles in lung injury repair in adult mice. Although there is considerable information known about these processes, the specific molecular pathways that mediate injury and regulate tissue repair are not fully elucidated. Using a hyperoxic injury model to study these mechanisms of lung injury and tissue repair, we selected the following genes based upon their known or putative roles in lung development and organogenesis: TTF-1, FGF9, FGF10, BMP4, PDGF-A, VEGF, Ptc, Shh, Sca-1, BCRP, CD45, and Cyclin-D2. Our findings demonstrate that several developmentally important genes (Sca-1, Shh, PDGF-A, VEGF, BCRP, CD45, BMP4, and Cyclin-D2) change during hyperoxic injury and normoxic recovery in mice, suggesting that adult lung may reactivate key developmental regulatory pathways for tissue repair. The mRNA for one gene (TTF-1), unchanged during hyperoxia, was upregulated late in recovery phase. These novel findings provide the basis for testing the efficacy of post-injury lung repair in animals genetically modified to inactivate or express individual molecules.
Pogach
Melanie S
MS
Pulmonary Center, Boston University, Boston, Massachusetts 02118, USA. mpogach@lung.bumc.bu.edu
Cao
Yuxia
Y
Millien
Guetchyn
G
Ramirez
Maria I
MI
Williams
Mary C
MC
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051525:Fibroblast Growth Factor 9 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018496:Hyperoxia / Q000503:physiopathology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000235:genetics* / Q000503:physiopathology; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D004268:DNA-Binding Proteins; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C465570:Shh protein, mouse; D014157:Transcription Factors; C504004:Ttf1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D017493:Leukocyte Common Antigens