Published ahead of print on March 5, 2003, doi:10.1164/rccm.200207-662OC Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1554-1561 A more recent version of this article appeared on June 1, 2003
Submitted on July 6, 2002 Fibroblast Growth Factor Receptor-1 and Neonatal Compensatory Lung Growth after 95% Oxygen ExposureRobert P Jankov1,1 Canadian Institute for Health Research Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Lung Biology Programme, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Physiology, University of Toronto, Toronto, Ontario, Canada, 2 Tongji Hospital and Tongji Medical College, Wuhan, China; Pediatrics, Huazhong University of Science and Technology, Wuhan, China; Lung Biology Programme, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada, 3 Canadian Institute for Health Research Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Lung Biology Programme, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada, 4 Canadian Institute for Health Research Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Physiology, University of Toronto, Toronto, Ontario, Canada; Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada, 5 Canadian Institute for Health Research Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Paediatrics, University of Toronto, Toronto, Ontario, Canada; Physiology, University of Toronto, Toronto, Ontario, Canada * To whom correspondence should be addressed. E-mail: keith.tanswell{at}sickkids.ca.
Neonatal rats exposed to 95% O2 for 7 days from birth had inhibited lung growth, DNA synthesis and secondary septation. These parameters were rapidly restored by a period of recovery in air. Northern and Western blot analysis and immunohistochemistry were used to screen for the fibroblast growth factor receptor-1 and its high affinity ligand, basic fibroblast growth factor, which could have a role in this recovery process. Expression of basic fibroblast growth factor in the lung was significantly reduced at the end of the 7-day exposure to 95% O2 and was increased after 3 days of recovery in air. Expression of fibroblast growth factor receptor-1 was not affected by exposure to 95% O2 or recovery in air. We hypothesized that the increase in basic fibroblast growth factor following removal from 95% O2, acting through the fibroblast growth factor receptor-1, would be critical for compensatory growth. Intraperitoneal injection of soluble truncated fibroblast growth factor receptor-1 at the onset of the recovery phase arrested compensatory lung DNA synthesis and secondary septation seen in control animals after 3 days of recovery, confirming a role for fibroblast growth factor receptor-1 in this model of compensatory neonatal lung growth. Key words: pulmonary oxygen toxicity, bronchopulmonary dysplasia, reactive oxygen species, soluble receptors
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