Up-regulation of connective tissue growth factor in hyperoxia-induced lung fibrosis.
Pulmonary oxygen toxicity plays an important role in the lung injury process that leads to the development of bronchopulmonary dysplasia. Connective tissue growth factor (CTGF) is a fibroblast mitogen and promoter of collagen deposition. We investigated the effects of postnatal hyperoxia on lung collagen and CTGF expression in rats. Rat pups were exposed to 7 d of >95% O2 and a further 3 wk of 60% O2. CTGF mRNA and protein expression increased after hyperoxia treatment, and the values were significantly higher in hyperoxia-exposed rats on postnatal d 7 and 14. Lung collagen levels increased as rats aged, and the values were comparable between room air-exposed and hyperoxia-exposed rats on postnatal d 7 and 14 and were significantly higher in hyperoxia-exposed rats on postnatal d 21 and 28. Increases in CTGF mRNA and protein expressions preceded the onset of increased lung collagen. These data demonstrate that CTGF is up-regulated at time points preceding the fibrotic phase of the lung injury adding credence to the hypothesis that CTGF seems to be involved in the pathogenesis of hyperoxia-induced lung fibrosis and an anti-CTGF strategy might attenuate hyperoxia-induced lung fibrosis.
Chen
Chung-Ming
CM
Department of Pediatrics, Taipei Medical University Hospital, Taiwan. cmchen@tmu.edu.tw
Wang
Leng-Fang
LF
Chou
Hsiu-Chu
HC
Lang
Yaw-Dong
YD
Lai
Yi-Ping
YP
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western; D001835:Body Weight; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010100:Oxygen; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D003094:Collagen; D010100:Oxygen