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Lithium attenuates TGF- β_1-induced fibroblasts to myofibroblasts transition in bronchial fibroblasts derived from asthmatic patients

By Marta Michalik, Katarzyna Wójcik-Pszczoła, Bogdan Jakieła, Katarzyna Piwowarczyk, Małgorzata Pierzchalska, Marek Sanak, Zbigniew Madeja and Jarosław Czyż

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-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

Publisher: 'Hindawi Limited'
Year: 2012
DOI identifier: 10.1155/2012/206109
OAI identifier: oai:ruj.uj.edu.pl:item/26555
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