[Effect of tyrosine kinase inhibitors on airway remodeling in bronchial asthma].
OBJECTIVE
To investigate the effect of tyrosine kinase inhibitors (TKIs) on asthmatic rat airway remodeling.


METHODS
The inhibitive effects of three TKIs (Genistein, jin-zhuan-ting and Tyrphostin AG1478) on proliferation of primary cultures of rat tracheal epithelial cells were assessed by MTT assay. Then, jin-zhuan-ting was adopted in the asthmatic rat model; immunohistofluorescene method was used to stain phosphorylated tyrosine (P-tyr) for disclosing the activation of EGFR; Sirius Red staining of submucosal collagen I and III was performed, and an analysis was made on the correlation between EGFR activation and collagen I and III deposition.


RESULTS
All the three TKIs inhibited the growth of tracheal epithelial cells in a time and dose depending manner, and the inhibition rates among them showed no statistical differences; airway subepithelial collagen I and III deposition degrees were markedly elevated in asthmatic groups and jin-zhuan-ting reduced the deposition in a certain degree; EGFR activation (P-tyr) in airways epithelium of asthmatic groups was greatly increased in comparison with that of control groups, and it was evidently decreased in jin-zhuan-ting groups. Correlation analysis demonstrated that the amount of airway subepithelial collagen I and III was positively correlated to EGFR activation.


CONCLUSIONS
TKIs may have preventive implications for asthmatic airway remodeling.
Long
Huai-cong
HC
Respiratory Ward of Gerontology Department, Sichuan People's Hospital, Chengdu 610072, China.
Wang
Zeng-li
ZL
Xiao
Bang-rong
BR
Wang
Gang
G
Wang
Zhang-hui
ZH
D000818:Animals; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000473:pathology* / Q000503:physiopathology; D020032:Tyrphostins / Q000494:pharmacology
D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases