Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts.

Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts. Toxicol Lett. 2013 Apr 22; Authors: Farid M, Kanaji N, Nakanishi M, Gunji Y, Michalski J, Iwasawa S, Ikari J, Wang X, Basma H, Nelson AJ, Liu X, Rennard SI Abstract Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), yet pathogenic mechanisms are not fully understood. Vascular endothelial growth factor (VEGF) is one of the major regulators of endothelial cell survival and is believed to play a role in the pathogenesis of COPD. Fibroblasts are a significant source of VEGF in the lungs; however the effect of cigarette smoke exposure on VEGF release by fibroblasts is not fully understood. We hypothesized that cigarette smoke-induced disturbed VEGF release by human lung fibroblasts is a potential pathogenic mechanism that could contribute to COPD. Cigarette smoke extract (CSE) was prepared by modification of the methods of Carp and Janoff (American Review of Respiratory Disease, 1978). Human fetal lung fibroblasts (HFL-1) were exposed to different concentrations of CSE and for different durations. VEGF release into the media was measured using ELISA. TGF-β1 receptor (TβR1)/Smad3 as a potential pathway for CSE modulated VEGF release was also investigated using biochemical analyses and siRNA inhibition of Smad3 and siRNA and pharmacologic inhibition of TβR1. CSE induced VEGF release by HFL-1 in concentration and ...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research