| http://purl.uniprot.org/citations/25848047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25848047 | http://www.w3.org/2000/01/rdf-schema#comment | "Idiopathic pulmonary fibrosis (IPF) is a devastating disease, and its pathogenic mechanisms remain incompletely understood. Peroxisomes are known to be important in ROS and proinflammatory lipid degradation, and their deficiency induces liver fibrosis. However, altered peroxisome functions in IPF pathogenesis have never been investigated. By comparing peroxisome-related protein and gene expression in lung tissue and isolated lung fibroblasts between human control and IPF patients, we found that IPF lungs exhibited a significant down-regulation of peroxisomal biogenesis and metabolism (e.g., PEX13p and acyl-CoA oxidase 1). Moreover, in vivo the bleomycin-induced down-regulation of peroxisomes was abrogated in transforming growth factor beta (TGF-β) receptor II knockout mice indicating a role for TGF-β signaling in the regulation of peroxisomes. Furthermore, in vitro treatment of IPF fibroblasts with the profibrotic factors TGF-β1 or tumor necrosis factor alpha (TNF-α) was found to down-regulate peroxisomes via the AP-1 signaling pathway. Therefore, the molecular mechanisms by which reduced peroxisomal functions contribute to enhanced fibrosis were further studied. Direct down-regulation of PEX13 by RNAi induced the activation of Smad-dependent TGF-β signaling accompanied by increased ROS production and resulted in the release of cytokines (e.g., IL-6, TGF-β) and excessive production of collagen I and III. In contrast, treatment of fibroblasts with ciprofibrate or WY14643, PPAR-α activators, led to peroxisome proliferation and reduced the TGF-β-induced myofibroblast differentiation and collagen protein in IPF cells. Taken together, our findings suggest that compromised peroxisome activity might play an important role in the molecular pathogenesis of IPF and fibrosis progression, possibly by exacerbating pulmonary inflammation and intensifying the fibrotic response in the patients."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1415111112"xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Zhang W."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Shi W."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Ruppert C."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Vijayan V."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Baumgart-Vogt E."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Karnati S."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Gunther A."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Boateng E."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Kotarkonda L.K."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/author | "Oruqaj G."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/pages | "E2048-57"xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/title | "Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-beta signaling."xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://purl.uniprot.org/core/volume | "112"xsd:string |
| http://purl.uniprot.org/citations/25848047 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25848047 |
| http://purl.uniprot.org/citations/25848047 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25848047 |
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| http://purl.uniprot.org/uniprot/#_A0A078BCJ0-mappedCitation-25848047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25848047 |
| http://purl.uniprot.org/uniprot/#_A0A078BCH8-mappedCitation-25848047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25848047 |
| http://purl.uniprot.org/uniprot/#_A0A078BFK3-mappedCitation-25848047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25848047 |