title: [Gefitinib inhibits α-smooth muscle actin expression in mice with bleomycin-induced lung fibrosis].
abstract: OBJECTIVE
  To evaluate the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, on the expression of α-smooth muscle actin (α-SMA) in mice with lung fibrosis induced by bleomycin.
  
  
  METHODS
  Thirty male BALB/c mice were randomly divided into control, bleomycin, and bleomycin plus gefitinib groups. The mice in the control group were subjected to intratracheal administration of normal saline, those in bleomycin group received bleomycin (3 mg/kg) intratracheally, and those in bleomycin plus gefitinib group received oral gefitinib (20 mg/kg administering) plus intratracheal bleomycin administration. All the mice were sacrificed 14 days after the treatments, and the left lung was examined pathologically with HE staining and Masson staining and also immunohistochemically for assay of the total EGFR, phosphorylated EGFR and α-SMA. The right lungs were sampled for RT-PCR to detect the mRNA levels of α-SMA.
  
  
  RESULTS
  Gefitinib administration lessened lung fibrosis induced by bleomycin and significantly reduced lung collagen accumulation. The phosphorylation of EGFR in the pulmonary mesenchymal cells and epithelial cells and the expression levels of α-SMA mRNA and protein were inhibited by gefitinib treatment in mice with intratracheal administration of bleomycin (P<0.05).
  
  
  CONCLUSIONS
  Gefitinib offers protection against lung fibrosis induced by bleomycin in mice probably by inhibiting the downstream signals of EGFR and by downregulating the expression of α-SMA.
authors.affiliation: Department of Respiratory Disease, Guangzhou General Hospital of Guangzhou Command, China. lili_china@163.com
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Yuan
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D066246:ErbB Receptors / Q000378:metabolism; D000077156:Gefitinib; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000199:Actins; D011799:Quinazolines; D012333:RNA, Messenger; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D000077156:Gefitinib