TY - JOUR
T1 - Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury
AU - Miranda, Luis F.
AU - Rodrigues, Claudia O.
AU - Ramachandran, Shalini
AU - Torres, Eneida
AU - Huang, Jian
AU - Klim, Jammie
AU - Hehre, Dorothy
AU - McNiece, Ian
AU - Hare, Joshua M.
AU - Suguihara, Cleide Y.
AU - Young, Karen C.
PY - 2013/12
Y1 - 2013/12
N2 - Background: Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. Methods: Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 μg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. Results: As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. Conclusion: Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis.
AB - Background: Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. Methods: Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 μg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. Results: As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. Conclusion: Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84890666094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890666094&partnerID=8YFLogxK
U2 - 10.1038/pr.2013.165
DO - 10.1038/pr.2013.165
M3 - Article
C2 - 24153399
AN - SCOPUS:84890666094
SN - 0031-3998
VL - 74
SP - 682
EP - 688
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -