Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 임재향 | * |
dc.date.accessioned | 2020-03-23T16:30:13Z | - |
dc.date.available | 2020-03-23T16:30:13Z | - |
dc.date.issued | 2020 | * |
dc.identifier.issn | 1421-9778 | * |
dc.identifier.other | OAK-26604 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/253599 | - |
dc.description.abstract | BACKGROUND/AIMS: Idiopathic pulmonary fibrosis (IPF) is a specific form of progressive and chronic interstitial lung disease of unknown cause. IPF is characterized by excessive deposition of extracellular matrix (ECM) and destructive pathological remodeling due to epithelial-to-mesenchymal transition (EMT). Eventually, lung interstitium thickens and stiffens and breathing becomes difficult. It has been well established that the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway plays a critical role in the pathogenesis of pulmonary fibrosis. TGF-β1-mediated activation of mitogen activated protein kinase (MAPK) family affects Smad signaling. p90RSK is a serine/threonine kinase and is activated by the extracellular signal-regulated kinase (ERK) signaling pathway. However, the roles played by p90RSK in TGF-β1 signaling and the pathogenesis of pulmonary fibrosis remain unknown. METHODS: We investigated whether p90RSK regulates the pathogenesis of pulmonary fibrosis using in vitro and in vivo systems and Western blotting, real-time quantitative PCR, transcriptional activity assays and immunofluorescence studies. RESULTS: Pharmacological inhibition of p90RSK by FMK or inhibition of p90RSK with adenoviral vector encoding a dominant negative form of p90RSK suppressed TGF-β1-induced ECM accumulation and EMT in lung epithelial cells and fibroblasts. Interestingly, FMK significantly inhibited TGF-β1-induced Smad3 nuclear translocation and smad binding element-dependent transcriptional activity, but not Smad3 phosphorylation. Furthermore, in a mouse model of bleomycin-induced lung fibrosis, FMK ameliorated pulmonary fibrosis. CONCLUSION: These findings indicate that p90RSK plays critical roles in pulmonary fibrosis, which suggests it be viewed as a novel therapeutic target for the treatment of lung fibrosis. © Copyright by the Author(s). Published by Cell Physiol Biochem Press. | * |
dc.language | English | * |
dc.publisher | NLM (Medline) | * |
dc.subject | Pulmonary fibrosis | * |
dc.subject | p90RSK | * |
dc.subject | TGF-β1 | * |
dc.subject | ECM | * |
dc.subject | EMT | * |
dc.title | p90RSK Inhibition Ameliorates TGF-β1 Signaling and Pulmonary Fibrosis by Inhibiting Smad3 Transcriptional Activity | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 54 | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 195 | * |
dc.relation.lastpage | 210 | * |
dc.relation.journaltitle | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | * |
dc.identifier.doi | 10.33594/000000214 | * |
dc.identifier.scopusid | 2-s2.0-85079789459 | * |
dc.author.google | Kim S. | * |
dc.author.google | Han J.-H. | * |
dc.author.google | Lee H. | * |
dc.author.google | Kim J.-R. | * |
dc.author.google | Lim J.H. | * |
dc.author.google | Woo C.-H. | * |
dc.contributor.scopusid | 임재향(7403454262) | * |
dc.date.modifydate | 20240429115530 | * |