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- W4206029362 abstract "Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss of trans-epithelial resistance (TER). Significantly, TGF-beta1-mediated EMT was markedly blunted in epithelial cells lacking JNK1, while JNK2-/- MTEC underwent EMT in response to TGF-beta1 in a similar way to wild-type cells. Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar in JNK1-/- MTEC in response to TGF-beta1, Smad DNA-binding activity was diminished. Gene expression profiling demonstrated a global suppression of TGF-beta1-modulated genes, including regulators of EMT in JNK1-/- MTEC, in comparison with wild-type cells. In aggregate, these results illuminate the novel role of airway epithelial-dependent JNK1 activation in EMT. PMID: 18334556 Funding information This work was supported by: PHS HHS, United States Grant ID: P20 RL 15557 NHLBI NIH HHS, United States Grant ID: R01 HL-079331 NHLBI NIH HHS, United States Grant ID: R01 HL-60014 NHLBI NIH HHS, United States Grant ID: R01 HL079331 Howard Hughes Medical Institute, United States NHLBI NIH HHS, United States Grant ID: R01 HL079331-01 NHLBI NIH HHS, United States Grant ID: R01 HL060014-01A1 NHLBI NIH HHS, United States Grant ID: R01 HL085464 NCRR NIH HHS, United States Grant ID: P20 RR015557-010002 NHLBI NIH HHS, United States Grant ID: R01 HL060014 NCRR NIH HHS, United States Grant ID: P20 RR015557 NHLBI NIH HHS, United States Grant ID: F32 HL082121 NHLBI NIH HHS, United States Grant ID: F32 HL-082121 More Less keyboard_arrow_down" @default.
- W4206029362 created "2022-01-25" @default.
- W4206029362 creator A5079249811 @default.
- W4206029362 date "2008-04-21" @default.
- W4206029362 modified "2023-09-27" @default.
- W4206029362 title "Faculty Opinions recommendation of Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1." @default.
- W4206029362 doi "https://doi.org/10.3410/f.1105114.561294" @default.
- W4206029362 hasPublicationYear "2008" @default.
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