[Effect of gefinitib on airway mucus hypersecretion induced by acrolein in rats].
OBJECTIVE
To test the effect of gefinitib, an EGFR-TKI, on airway mucus hypersecretion induced by acrolein in rats.


METHODS
Thirty six rats were randomly divided into six groups, each with six rats. Group A did not get any intervention; group B had airway mucus hypersecretion induced by inhaled acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of 10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively, 30 min before exposure to acrolein inhalation; group F served as a control group, with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline inhalation. After three weeks, the rats were sacrificed. The lung tissue sections were obtained. The immunohistochemistry and RT-PCR were performed to detect the MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff (AB-PAS).


RESULTS
Overexpression of MUC5AC, EGFR and increased goblet cells in the lungs of the rats were found in the rats exposed to acrolein inhalations. Gefitinib intervention inhibited the expression of MUC5AC and the increase of goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR in the lungs.


CONCLUSIONS
Acrolein increases the expression of MUC5AC through activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in the treatment of mucus hypersecretion by regulating the signal transduction pathways of EGFR.
Guan
Aiu-Yue
AY
Department of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
Xu
Zhi-Bo
ZB
Wen
Fu-Qiang
FQ
Wang
Bo-Ding
BD
Feng
Yu-Lin
YL
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D055271:Mucin 5AC / Q000096:biosynthesis / Q000235:genetics; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000171:Acrolein; D066246:ErbB Receptors; D000077156:Gefitinib