title: Lithium Attenuates TGF-β(1)-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients.
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-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β(1)-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β 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.
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Michalik
authors.forename: Katarzyna Anna
authors.initials: KA
authors.lastname: Wójcik
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakieła
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szpak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Pierzchalska
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
authors.forename: Jarosław
authors.initials: J
authors.lastname: Czyż