Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients. (3rd September 2012)

• Record Type: Journal Article
• Authors: Michalik, Marta; Wójcik, Katarzyna Anna; Jakieła, Bogdan; Szpak, Katarzyna; Pierzchalska, Małgorzata; Sanak, Marek; Madeja, Zbigniew; Czyż, Jarosław
• Other Names: Leung Ting Fan Academic Editor.
• Is Part Of: Journal of allergy. Volume 2012(2012)
• Publication Date: 2012-09-03
• Subjects: Allergy -- Periodicals; Immunologic diseases -- Periodicals; Allergy and Immunology; Hypersensitivity; Immune System Diseases; Allergy; Immunologic diseases; Electronic journals; Periodical; Periodicals; 616.97
• DOI: 10.1155/2012/206109
• Languages: English
• ISSNs: 1687-9783

Abstract

Abstract : 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-3 β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3 β inhibitor, on TGF- β 1 -induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3 β attenuates TGF- β 1 -induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β -catenin, abundant in TGF- β 1 /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.