Connective tissue growth factor expression is upregulated in hyperoxia-induced lung fibrosis
Chung-Ming Chen1, Leng-Fang Wang2, and Hsiu-Chu Chou3
1Department of Pediatrics, Taipei Medical University Hospital; 2Departments of 2Biochemistry
and 3Anatomy, Taipei Medical University, Taipei, Taiwan
Background: Bronchopulmonary dysplasia is characterized by decreased alveolar development and fibrosis and develops in newborn infants treated with oxygen and positive pressure ventilation for respiratory distress at birth. The accumulation of connective tissue is controlled by connective tissue growth factor (CTGF).
Objective: To establish an animal model of lung fibrosis induced by hyperoxia and to evaluate the role of CTGF in the pathogenesis of hyperoxia-induced lung fibrosis.
Design/Methods: Within 12 h of birth, pups were randomly redistributed to the newly delivered Sprague-Dawley dams and exposed to 7 days of >95% O2 and then were allowed to
recover from the acute injury in a continuing environment of moderate hyperoxia (60% O2) for
a further 3 wks. Control rats were kept in room air for 4 wks. Lung tissue from control and hyperoxia-exposed pups were harvested on postnatal days 7, 14, 21, and 28. Lung CTGF expression and total collagen was measured using real time PCR and Sircol dye method, respectively. Lung tissue was examined by H&E and TUNEL stains.
Results: Rats exposed to hyperoxia exhibited significantly lower body weight on postnatal days 7, 14, and 21. Lung/body weight ratio was significantly lower on postnatal day 7 and significantly higher on postnatal days 14 and 21 in hyperoxia-exposed rats when compared with control rats. Hyperoxia significantly increased CTGF expression on postnatal days 7 and 14 and total lung collagen content on postnatal days 21 and 28. Hyperoxia-exposed rats had significantly higher apoptotic alveolar cells on postnatal days 7, 14, 21 and 28 and revealed less developed alveoli and increased lung fibrosis.
Conclusions: Hyperoxia arrests alveolar development and increases CTGF expression and total collagen contents in postnatal rat lungs. These data demonstrate that CTGF may play a role in the pathogenesis of hyperoxia-induced lung fibrosis and provide useful therapeutic strategies to treat pulmonary fibrosis.
