| http://purl.uniprot.org/citations/26816051 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26816051 | http://www.w3.org/2000/01/rdf-schema#comment | "Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, has been linked to endoplasmic reticulum (ER) stress. To investigate a causal role for ER stress in BPD pathogenesis, we generated conditional knockout (KO) mice (cGrp78(f/f)) with lung epithelial cell-specific KO of Grp78, a gene encoding the ER chaperone 78-kD glucose-regulated protein (GRP78), a master regulator of ER homeostasis and the unfolded protein response (UPR). Lung epithelial-specific Grp78 KO disrupted lung morphogenesis, causing developmental arrest, increased alveolar epithelial type II cell apoptosis, and decreased surfactant protein and type I cell marker expression in perinatal lungs. cGrp78(f/f) pups died immediately after birth, likely owing to respiratory distress. Importantly, Grp78 KO triggered UPR activation with marked induction of the proapoptotic transcription factor CCAAT/enhancer-binding proteins (C/EBP) homologous protein (CHOP). Increased expression of genes involved in oxidative stress and cell death and decreased expression of genes encoding antioxidant enzymes suggest a role for oxidative stress in alveolar epithelial cell (AEC) apoptosis. Increased Smad3 phosphorylation and expression of transforming growth factor-β/Smad3 targets Cdkn1a (encoding p21) and Gadd45a suggest that interactions among the apoptotic arm of the UPR, oxidative stress, and transforming growth factor-β/Smad signaling pathways contribute to Grp78 KO-induced AEC apoptosis and developmental arrest. Chemical chaperone Tauroursodeoxycholic acid reduced UPR activation and apoptosis in cGrp78(f/f) lungs cultured ex vivo, confirming a role for ER stress in observed AEC abnormalities. These results demonstrate a key role for GRP78 in AEC survival and gene expression during lung development through modulation of ER stress, and suggest the UPR as a potential therapeutic target in BPD."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.org/dc/terms/identifier | "doi:10.1165/rcmb.2015-0327oc"xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Zhou B."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Lee A.S."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Laird-Offringa I.A."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Flodby P."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Marconett C.N."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/author | "Minoo P."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/name | "Am J Respir Cell Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/pages | "135-149"xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/title | "The 78-kD Glucose-Regulated Protein Regulates Endoplasmic Reticulum Homeostasis and Distal Epithelial Cell Survival during Lung Development."xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://purl.uniprot.org/core/volume | "55"xsd:string |
| http://purl.uniprot.org/citations/26816051 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26816051 |
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