title: Upregulation of gelatinases and epithelial-mesenchymal transition in small airway remodeling associated with chronic exposure to wood smoke.
abstract: BACKGROUND
  Peribronchiolar fibrosis is an important feature of small airway remodeling (SAR) in cigarette smoke-induced COPD. The aim of this study was to investigate the role of gelatinases (MMP9, MMP2) and epithelial-mesenchymal transition (EMT) in SAR related to wood smoke (WS) exposure in a rat model.
  
  
  METHODS
  Forty-eight female Sprague-Dawley rats were randomly divided into the WS group, the cigarette smoke (CS) group and the clean air control group. After 4 to 7 months of smoke exposure, lung tissues were examined with morphometric measurements, immunohistochemistry and Western blotting. Serum MMP9 and TIMP1 concentrations were detected by ELISA. In vitro, primary rat tracheal epithelial cells were stimulated with wood smoke condensate for 7 days.
  
  
  RESULTS
  The COPD-like pathological alterations in rats exposed chronically to WS were similar to those exposed to CS; the area of collagen deposition was significantly increased in the small airway walls of those exposed to WS or CS for 7 months. The expression of gelatinases in rats induced by WS or CS exposure was markedly increased in whole lung tissue, and immunohistochemistry showed that MMP9, MMP2 and TIMP1 were primarily expressed in the airway epithelium. The serum levels of MMP9 and TIMP1 were significantly higher in rats secondary to WS or CS exposure. Few cells that double immunostained for E-cadherin and vimentin were observed in the airway subepithelium of rats exposed to WS for 7 months (only 3 of these 8 rats). In vitro, the expression of MMP9 and MMP2 proteins was upregulated in primary rat tracheal epithelial cells following exposure to wood smoke condensate for 7 days by Western blotting; positive immunofluorescent staining for vimentin and type I collagen was also observed.
  
  
  CONCLUSIONS
  These findings suggest that the upregulation of gelatinases and EMT might play a role in SAR in COPD associated with chronic exposure to wood smoke.
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Shaoxing
authors.initials: S
authors.lastname: Li
authors.affiliation: Guangzhou Chest Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zou
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Gongyong
authors.initials: G
authors.lastname: Peng
authors.affiliation: The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D002478:Cells, Cultured; D004781:Environmental Exposure; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism; D014026:Nicotiana / Q000737:chemistry; D015854:Up-Regulation; D014934:Wood / Q000737:chemistry*
chemical_list: D012906:Smoke; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9