[The effect of transcription factor KLF2 in expression of gamma-GCS depend on regulation by Nrf2 in lung of rats with chronic obstructive pulmonary disease].
OBJECTIVE
To study the expression of lung Krüppel-like transcription factor (KLF2/LKLF) in lung tissues of rats with chronic obstructive pulmonary disease (COPD) and the relationship between KLF2 and NF-E2-related factor 2 (Nrf2), and make further explore the effects of KLF2 on the expression of gamma-glutamylcysteine synthetase (gamma-GCS).


METHODS
Twenty-two male SD rats were randomly divided into a COPD group (n = 10) and a normal control group (n = 11). The rat model of COPD established by cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS), and lung tissues were obtained. The expressions of KLF2, Nrf2, gamma-GCS mRNA and protein in lung tissues were measured by immunohistochemistry (IHC), Western blot, in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). To explore the relationship between KLF2 and Nrf2 protein,we utilize the method of co-immunoprecipitation (CO-IP).


RESULTS
IHC and Western blot showed that protein expressions of KLF2, Nrf2, gamma-GCS were higher in the lung tissues from rats with COPD than those in the control groups (all P < 0.05). The levels of KLF2, gamma-GCS mRNA were markedly increased in the COPD group (all P < 0.01) while Nrf2 mRNA expression in COPD group had no significant difference with that in control group ( P > 0.05). CO-IP result showed that KLF2 were obviously present in immunoprecipitates of Nrf2 (P < 0.01) . Linear correlation analysis showed that the level of KLF2 protein was positively correlated with the level of Nrf2 protein (P < 0.05), and KLF2, Nrf2 proteins were positively correlated with gamma-GCS mRNA and protein (all P < 0.05).


CONCLUSIONS
The expression of KLF2 is significantly up-regulated in COPD, which maybe up-regulate gamma-GCS mRNA expression by increasing Nrf2 expression and nuclear translocation against oxidative stress.
Department of Respiratory Disease, Hunan Institute of Gerontology, Hunan Geriatric Hospital, Changsha 410016, China.
Xiao-Yan
XY
Liu
Ai-Guo
AG
Dai
Rui-Cheng
RC
Hu
Li-Ming
LM
Zhu
Shuang-Xiang
SX
Tan
D000818:Animals; D004151:Dipeptides / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004151:Dipeptides; C543921:Klf2 protein, rat; D051741:Kruppel-Like Transcription Factors; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C017341:gamma-glutamylcysteine