التفاصيل البيبلوغرافية
| العنوان: |
A Non-canonical Pathway with Potential for Safer Modulation of Transforming Growth Factor-beta 1 in Steroid-Resistant Airway Diseases |
| المؤلفون: |
Li, M, Keenan, CR, Lopez-Campos, G, Mangum, JE, Chen, Q, Prodanovic, D, Xia, YC, Langenbach, SY, Harris, T, Hofferek, V, Reid, GE, Stewart, AG |
| بيانات النشر: |
CELL PRESS |
| سنة النشر: |
2019 |
| المجموعة: |
The University of Melbourne: Digital Repository |
| الوصف: |
Impaired therapeutic responses to anti-inflammatory glucocorticoids (GC) in chronic respiratory diseases are partly attributable to interleukins and transforming growth factor β1 (TGF-β1). However, previous efforts to prevent induction of GC insensitivity by targeting established canonical and non-canonical TGF-β1 pathways have been unsuccessful. Here we elucidate a TGF-β1 signaling pathway modulating GC activity that involves LIM domain kinase 2-mediated phosphorylation of cofilin1. Severe, steroid-resistant asthmatic airway epithelium showed increased levels of immunoreactive phospho-cofilin1. Phospho-cofilin1 was implicated in the activation of phospholipase D (PLD) to generate the effector(s) (lyso)phosphatidic acid, which mimics the TGF-β1-induced GC insensitivity. TGF-β1 induction of the nuclear hormone receptor corepressor, SMRT (NCOR2), was dependent on cofilin1 and PLD activities. Depletion of SMRT prevented GC insensitivity. This pathway for GC insensitivity offers several promising drug targets that potentially enable a safer approach to the modulation of TGF-β1 in chronic inflammatory diseases than is afforded by global TGF-β1 inhibition. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
2589-0042 |
| Relation: |
NHMRC/1059665; NHMRC/1137171; pii: S2589-0042(19)30024-0; Li, M., Keenan, C. R., Lopez-Campos, G., Mangum, J. E., Chen, Q., Prodanovic, D., Xia, Y. C., Langenbach, S. Y., Harris, T., Hofferek, V., Reid, G. E. & Stewart, A. G. (2019). A Non-canonical Pathway with Potential for Safer Modulation of Transforming Growth Factor-beta 1 in Steroid-Resistant Airway Diseases. ISCIENCE, 12, pp.232-+. https://doi.org/10.1016/j.isci.2019.01.023.; http://hdl.handle.net/11343/253784 |
| الاتاحة: |
http://hdl.handle.net/11343/253784 |
| Rights: |
CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0 |
| رقم الانضمام: |
edsbas.7ECE7F43 |
| قاعدة البيانات: |
BASE |
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