Objective To investigate the expression and localization of activating transcription factor 3 ( ATF3) and ATF4 in lung of rats with chronic obstructive pulmonary disease ( COPD) , and explore their possible roles in the pathogenesis of COPD. Methods Twenty-two SD rats were randomly divided into a COPD group and a control group. The COPD model was established by cigarette smoking and intratracheal instillation of lipopolysaccharide. The lung function was measured and the pathological changes were observed under light microscope. In situ hybridization, reverse transcription-polymerase chain reaction ( RTPCR), immunohistochemistry, and Western blot techniques were used to detect the mRNA and protein expressions of ATF3 and ATF4 in rat lung. Results The lung function of the COPD group was significantlydecreased. The rats in the COPD group shared specific pathological features of COPD. Immunohistochemical and Western blot results showed that the protein expressions of ATF3 and ATF4 were higher in the COPD group than those in the control group ( P lt;0. 05) . In situ hybridization and RT-PCR results showed that themRNA expressions of ATF3 and ATF4 in the COPD group were also significantly higher than those in the control group ( P lt;0. 05) . Conclusions The expressions of ATF3 and ATF4 are significantly up-regulated in COPD. These findings suggest that ATF3 and ATF4 may play important roles in the oxidative and antioxidative imbalance in the pathogenesis of COPD.
Objective To investigate the expressions of activating transcription factor 3 (ATF3) and ATF4, and their effects on γ-glutamylcysteine synthetase (γ-GCS) in lung tissues of patients with chronic obstructive pulmonary disease (COPD). Methods Non-cancerous lung tissue specimens ( 5 cm or above away from tumor) were collected from 40 lung cancer patients who underwent pulmonary lobectomy between December 2008 and December 2009. The patients were divided into a COPD group and a control group according to whether they were complicated with COPD. The clinical data were collected including the history in detail, physical examination, chest X-ray or lung CT, and pulmonary function test. The mRNA and protein expressions of ATF3, ATF4, and heavy subunit of γ-GCS (γ-GCS-HS) in lung tissues were detected by in situ hybridization and immunohistochemistry. At the same time, the interaction between ATF3, ATF4 and γ-GCS-HS protein was investigated by co-immunoprecipitation method. The correlation of ATF3 and ATF4 with γ-GCS-HS was analyzed. Results The mRNA and protein expressions of ATF3, ATF4 and γ-GCS-HS in lung tissues of the COPD group were strongly positive, and significantly higher than those in the control group (P＜0.01). The co-immunoprecipitation showed that ATF3 and ATF4 antibodies could cross the clear protein bands in the immune precipitation captured by γ-GCS-HS, and the intensity in the COPD group was significantly enhanced than that in the control group (P＜0.01). Correlation analysis showed that the protein expressions of ATF3 and ATF4 were significantly positively correlated with the mRNA and protein expression of γ-GCS-HS (allP＜0.01). The protein expressions of ATF3, ATF4 and γ-GCS-HS in lung tissues were positively correlated with FEV1%pred and FEV/FVC (P＜0.01). Conclusions Oxidative stress induces overexpression of ATF3 and ATF4 which may paly role in the pathogenesis of COPD. ATF3 and ATF4 may play antioxidative effect by affecting the mRNA and protein expression of γ-GCS.