SMAD-signaling in chronic obstructive pulmonary disease: transcriptional down-regulation of inhibitory SMAD 6 and 7 by cigarette smoke
-
J. Springer
Abstract
Transforming growth factor-β1 is a potent mediator of fibrosis stimulating the secretion of extracellular matrix proteins and is involved in airway remodeling in chronic obstructive pulmonary disease (COPD). Signals from the TGF superfamily are mediated by the SMAD group of transcription factors. Here, the expression of the regulatory SMAD2, 3, the co-SMAD4 and the inhibitory SMAD6 and 7 was assessed in bronchial biopsies of COPD patients and controls by quantitative RTPCR. While SMAD2 was not expressed and SMAD3 and 4 displayed no change, the inhibitory SMAD6 and 7 were significantly downregulated in COPD. To reveal the molecular basis of tobacco smoke-induced airway remodeling and to test whether it may interfere with intracellular SMAD signaling, the airway epithelial cell line A549 was incubated with cigarette smoke extract (1% and 10%) for 48 hours, which led to down-regulation of SMAD6 and 7 at both concentrations tested. It can be concluded that TGF-β-mediated effects in COPD are influenced by a disturbed intracellular feedback mechanism of inhibitory SMADs. Also, the effects of non-volatile components in tobacco smoke may partly be regulated via a smoke-induced down-regulation of inhibitory SMADs.
Copyright © 2004 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- 55th Mosbach Colloquium: How nutrients influence gene activity
- Nutrient-gene interactions: a single nutrient and hundreds of target genes
- Regulation of gene expression by α-tocopherol
- Linking nutrition to genomics
- Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison
- All-trans retinoic acid-responsive genes identified in the human SH-SY5Y neuroblastoma cell line and their regulated expression in the nervous system of early embryos
- GAPDH enhances group II intron splicing in vitro
- Metal-responsive transcription factor-1 (MTF-1) selects different types of metal response elements at low vs. high zinc concentration
- Inactivation of protein disulfide isomerase by alkylators including α,β-unsaturated aldehydes at low physiological pHs
- Cell type-dependent release of nitric oxide and/or reactive nitrogenoxide species from intracellular SIN-1: effects on cellular NAD(P)H
- SMAD-signaling in chronic obstructive pulmonary disease: transcriptional down-regulation of inhibitory SMAD 6 and 7 by cigarette smoke
- Exogenously added GPI-anchored tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) displays enhanced and novel biological activities
- Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells
Articles in the same Issue
- 55th Mosbach Colloquium: How nutrients influence gene activity
- Nutrient-gene interactions: a single nutrient and hundreds of target genes
- Regulation of gene expression by α-tocopherol
- Linking nutrition to genomics
- Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison
- All-trans retinoic acid-responsive genes identified in the human SH-SY5Y neuroblastoma cell line and their regulated expression in the nervous system of early embryos
- GAPDH enhances group II intron splicing in vitro
- Metal-responsive transcription factor-1 (MTF-1) selects different types of metal response elements at low vs. high zinc concentration
- Inactivation of protein disulfide isomerase by alkylators including α,β-unsaturated aldehydes at low physiological pHs
- Cell type-dependent release of nitric oxide and/or reactive nitrogenoxide species from intracellular SIN-1: effects on cellular NAD(P)H
- SMAD-signaling in chronic obstructive pulmonary disease: transcriptional down-regulation of inhibitory SMAD 6 and 7 by cigarette smoke
- Exogenously added GPI-anchored tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) displays enhanced and novel biological activities
- Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells
