Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients
| Autor: | Marta Michalik, Bogdan Jakiela, Zbigniew Madeja, Katarzyna Szpak, Jarosław Czyż, Malgorzata Pierzchalska, Katarzyna Wójcik, Marek Sanak |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Journal of Allergy. 2012:1-12 |
| ISSN: | 1687-9791 1687-9783 |
| DOI: | 10.1155/2012/206109 |
| Popis: | Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases. |
| Databáze: | OpenAIRE |
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