Song, Dae-Geun Kim, Doyeun Jung, Jae Woo Nam, Seo Hee Kim, Ji Eon Kim, Hye-Jin Kim, Jong Hyun Pan, Cheol-Ho Kim, Sunghoon Lee, Jung Weon 2024-01-19T21:30:44Z 2024-01-19T21:30:44Z 2021-09-05 2018-11-20 1663-9812 https://pubs.kist.re.kr/handle/201004/120671 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. English FRONTIERS MEDIA SA MYOFIBROBLAST DIFFERENTIATION ACTIVATION PATHOGENESIS PATHWAY STAT3 Glutamyl-Prolyl-tRNA Synthetase Regulates Epithelial Expression of Mesenchymal Markers and Extracellular Matrix Proteins: Implications for Idiopathic Pulmonary Fibrosis Article 10.3389/fphar.2018.01337 1 FRONTIERS IN PHARMACOLOGY, v.9 FRONTIERS IN PHARMACOLOGY 9 scie scopus 000450696600001 2-s2.0-85057785016 Pharmacology & Pharmacy Pharmacology & Pharmacy Article MYOFIBROBLAST DIFFERENTIATION ACTIVATION PATHOGENESIS PATHWAY STAT3 idiopathic pulmonary fibrosis bleomycin fibrotic animal model extracellular matrix prolyl-tRNA-synthetase signal transduction STAT6