BackgroundPeribronchiolar 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.MethodsForty-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.ResultsThe 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.ConclusionsThese findings suggest that the upregulation of gelatinases and EMT might play a role in SAR in COPD associated with chronic exposure to wood smoke.
2058PENG G et al.
Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp arterial remodeling, less attention has been paid to the PV side in searching for the cellular and molecular mechanism of chronically hypoxic pulmonary venous remodeling.
Editorial p 1910In pulmonary vascular smooth muscle cells, the increase in intracellular Ca 2+ concentration ([Ca 2+ ]i) is an essential signal for vasoconstriction and myocyte proliferation. The elevation of [Ca 2+ ]i could result from Ca 2+ influx from an extracellular source through Ca 2+ channels, such as L-type voltage-dependent Ca 2+ channels (VDCC), store-operated Ca 2+ channels (SOCC) and receptor-operated Ca 2+ channels (ROCC), or Ca 2+ release from internal storage sites, such as the sarcoplasmic ulmonary veins (PV) not only serve as conduits through which oxygenated capillary blood drains into the left atrium of the heart in pulmonary circulation, but they also play important roles in regulating both distention and recruitment of blood flow from alveolar wall capillaries and thus ventilation-perfusion matching in the lung. Studies reveal that PV exhibit vasoconstriction in response to various vasoconstrictor stimuli, such as endothelin, thromboxane, plateletactivating factor, leukotrienes and hypoxia. Exposure to chronic hypoxia (CH) causes vascular remodeling not only in pulmonary arteries (PA) but also in PV in a number of species including rat, sheep and humans, 1-4 and leads to hypoxic pulmonary hypertension (HPH). Despite the numerous progresses in elucidating the underlying mechanisms of CH-induced pulmonary
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