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Glutamyl-prolyl-tRNA synthetase regulates epithelial expression of mesenchymal markers and extracellular matrix proteins: Implications for idiopathic pulmonary fibrosis
DC Field | Value | Language |
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dc.contributor.author | Song, Dae-Geun | - |
dc.contributor.author | Kim, Doyeun | - |
dc.contributor.author | Jung, Jae Woo | - |
dc.contributor.author | Nam, Seo Hee | - |
dc.contributor.author | Kim, Ji Eon | - |
dc.contributor.author | Kim, Hye-Jin | - |
dc.contributor.author | Kim, Jong Hyun | - |
dc.contributor.author | Pan, Cheol-Ho | - |
dc.contributor.author | Kim, Sunghoon | - |
dc.contributor.author | Lee, Jung Weon | - |
dc.creator | 이정원 | - |
dc.date.accessioned | 2019-04-25T02:05:55Z | - |
dc.date.available | 2020-04-05T02:05:55Z | - |
dc.date.created | 2019-07-03 | - |
dc.date.issued | 2018-11 | - |
dc.identifier.citation | Frontiers in Pharmacology, Vol.9, p. 01337 | - |
dc.identifier.issn | 1663-9812 | - |
dc.identifier.uri | https://hdl.handle.net/10371/150174 | - |
dc.description.abstract | Idiopathic pulmonary fibrosis (IPF), a chronic disease of unknown cause, is characterized by abnormal accumulation of extracellular matrix (ECM) in fibrotic foci in the lung. Previous studies have shown that the transforming growth factor beta 1 (TGF beta 1) and signal transducers and activators of transcription (STAT) pathways play roles in IPF pathogenesis. Glutamyl-prolyl-tRNA-synthetase (EPRS) has been identified as a target for anti-fibrosis therapy, but the link between EPRS and TGF beta 1-mediated IPF pathogenesis remains unknown. Here, we studied the role of EPRS in the development of fibrotic phenotypes in A549 alveolar epithelial cells and bleomycin-treated animal models. We found that EPRS knockdown inhibited the TGF beta 1-mediated upregulation of fibronectin and collagen I and the mesenchymal proteins alpha-smooth muscle actin (alpha-SMA) and snail 1. TGF beta 1-mediated transcription of collagen I-alpha 1 and laminin gamma 2 in A549 cells was also down-regulated by EPRS suppression, indicating that EPRS is required for ECM protein transcriptions. Activation of STAT signaling in TGF beta 1-induced ECM expression was dependent on EPRS. TGF beta 1 treatment resulted in EPRS-dependent in vitro formation of a multi-protein complex consisting of the TGF beta 1 receptor, EPRS, Janus tyrosine kinases (JAKs), and STATs. In vivo lung tissue from bleomycin-treated mice showed EPRS-dependent STAT6 phosphorylation and ECM production. Our results suggest that epithelial EPRS regulates the expression of mesenchymal markers and ECM proteins via the TGF beta 1/STAT signaling pathway. Therefore, epithelial EPRS can be used as a potential target to develop anti-IPF treatments. | - |
dc.language | 영어 | - |
dc.language.iso | en | en |
dc.publisher | Frontiers Media S.A. | - |
dc.title | Glutamyl-prolyl-tRNA synthetase regulates epithelial expression of mesenchymal markers and extracellular matrix proteins: Implications for idiopathic pulmonary fibrosis | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fphar.2018.01337 | - |
dc.citation.journaltitle | Frontiers in Pharmacology | - |
dc.identifier.wosid | 000450696600001 | - |
dc.identifier.scopusid | 2-s2.0-85057785016 | - |
dc.description.srnd | OAIID:RECH_ACHV_DSTSH_NO:T201812085 | - |
dc.description.srnd | RECH_ACHV_FG:RR00200001 | - |
dc.description.srnd | ADJUST_YN: | - |
dc.description.srnd | EMP_ID:A078142 | - |
dc.description.srnd | CITE_RATE:3.831 | - |
dc.description.srnd | FILENAME:105-DGS-FIP.pdf | - |
dc.description.srnd | DEPT_NM:약학과 | - |
dc.description.srnd | EMAIL:jwl@snu.ac.kr | - |
dc.description.srnd | SCOPUS_YN:Y | - |
dc.description.srnd | FILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/32495e8d-584a-4be0-90f9-804bfdffbf0b/link | - |
dc.citation.startpage | 01337 | - |
dc.citation.volume | 9 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Lee, Jung Weon | - |
dc.identifier.srnd | T201812085 | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | MYOFIBROBLAST DIFFERENTIATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | STAT3 | - |
dc.subject.keywordAuthor | idiopathic pulmonary fibrosis | - |
dc.subject.keywordAuthor | bleomycin fibrotic animal model | - |
dc.subject.keywordAuthor | extracellular matrix | - |
dc.subject.keywordAuthor | prolyl-tRNA-synthetase | - |
dc.subject.keywordAuthor | signal transduction | - |
dc.subject.keywordAuthor | STAT6 | - |
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