TY - JOUR
T1 - High tidal volume ventilation activates Smad2 and upregulates expression of connective tissue growth factor in newborn rat lung
AU - Wu, Shu
AU - Capasso, Letizia
AU - Lessa, Andrea
AU - Peng, Jinghong
AU - Kasisomayajula, Kalyani
AU - Rodriguez, Maria
AU - Suguihara, Cleide
AU - Bancalari, Eduardo
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/3
Y1 - 2008/3
N2 - High tidal volume (VT) ventilation plays a key role in ventilator induced lung injury and bronchopulmonary dysplasia. However, little is known about the effect of high VT on expression of growth factors that are critical to lung development. In a previous study, we demonstrated that connective tissue growth factor (CTGF) inhibits branching morphogenesis. In this study, we investigated the effect of high VT on CTGF expression in newborn rat lungs. Newborn rats were ventilated with normal VT (10 mL/kg) or high VT (25 mL/kg) for 6 h. Nonventilated animals served as controls. We found that high VT upregulated CTGF expression. To identify the potential signaling pathways mediating high VT induction of CTGF, newborn rats were ventilated with high VT for 1 or 3 h. Temporal expression of TGF-βs, p-Smad2, Smad7, and CTGF was analyzed. High VT ventilation did not change gene expression of TGF-βs and Smad7 but induced rapid and sustained expression of p-Smad2 that precedes increased CTGF expression. CTGF and p-Smad2 were localized in bronchiolar epithelial cells, alveolar walls and septa. These data suggest that high Vt ventilation activates the Smad2 pathway, which may be responsible for downstream induction of CTGF expression in newborn rat lungs.
AB - High tidal volume (VT) ventilation plays a key role in ventilator induced lung injury and bronchopulmonary dysplasia. However, little is known about the effect of high VT on expression of growth factors that are critical to lung development. In a previous study, we demonstrated that connective tissue growth factor (CTGF) inhibits branching morphogenesis. In this study, we investigated the effect of high VT on CTGF expression in newborn rat lungs. Newborn rats were ventilated with normal VT (10 mL/kg) or high VT (25 mL/kg) for 6 h. Nonventilated animals served as controls. We found that high VT upregulated CTGF expression. To identify the potential signaling pathways mediating high VT induction of CTGF, newborn rats were ventilated with high VT for 1 or 3 h. Temporal expression of TGF-βs, p-Smad2, Smad7, and CTGF was analyzed. High VT ventilation did not change gene expression of TGF-βs and Smad7 but induced rapid and sustained expression of p-Smad2 that precedes increased CTGF expression. CTGF and p-Smad2 were localized in bronchiolar epithelial cells, alveolar walls and septa. These data suggest that high Vt ventilation activates the Smad2 pathway, which may be responsible for downstream induction of CTGF expression in newborn rat lungs.
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U2 - 10.1203/PDR.0b013e318163a8cc
DO - 10.1203/PDR.0b013e318163a8cc
M3 - Article
C2 - 18287961
AN - SCOPUS:39749182824
VL - 63
SP - 245
EP - 250
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 3
ER -