Role of TGF-b1 in type I collagen production in bronchial epithelial cells: effects on Smad7 inhibitory role?

Giampiero La Rocca, Francesca Magno

Risultato della ricerca: Other

Abstract

Airway epithelial cells play an important role in inflammatory, apoptotic and remodelling process associate with fibrosis and COPD. Transforming growth factor 1 (TGF-b1) is involved in airways remodelling by Smads signalling pathway. We investigated the role of TGF-b1 on type I collagen production and Smads (Smad 2-3-4-and 7) expression in bronchial epithelial cells (16HBE). Cells were treated with 1ng/ml and 10ng/ml of TGF-b1 for 0, 3 and 24 hours. With low dose of TGF-b1 we observed no significant variation on Smad2 mRNA expression for both times but a significant increased of Smad7 mRNA expression at 3h (p=0.0043) and a significant reduction of Smad3, Smad4 and Smad7 mRNA expression at 24h of treatment (p=0.0207, p=0.0381 and p=0.0087, respectively); TGF-b1 increases type I collagen mRNA expression (p=0.0190), but no significantly Smad3 activation after just 3 hours of treatment (p=0.0571). High dose of TGF-b1 increases Smad2 mRNA expression at 3h (p=0.0190), Smad3 and Smad4 mRNA (p=0.0081, p=0.0087, respectively) and type I collagen mRNA at 24h (p=0.00022); no change were observed on Smad7 mRNA level. Than we observed a time dependent phospho-Smad3 significant increase (p= 0.0286 for 3 and 24h) but a phospho-Smad2 expression reduction.These results let think that TGF-b1 is involved on type I collagen production in 16HBE in a time and dose-dependent manner and this effect is mediated more by phosphor-Smad3 than phosphor-Smad2. These data shows that low doses of TGF-b1 had not effect on inhibitor Smad7 mechanism whom balances and reduces Smad3 activation and type I collagen production, while high doses seems act on inhibitor Smad7 mRNA expression with increase on phospho-Smad3 and type I collagen expression in 16HBE.
Lingua originaleEnglish
Pagine108-108
Numero di pagine1
Stato di pubblicazionePublished - 2008

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