TY - JOUR
T1 - Postpneumonectomy lung expansion elicits hypoxia-inducible factor-1α signaling
AU - Zhang, Quiyang
AU - Bellotto, Dennis J.
AU - Ravikumar, Priya
AU - Moe, Orson W.
AU - Hogg, Richard T.
AU - Hogg, Deborah C.
AU - Estrera, Aaron S.
AU - Johnson, Robert L.
AU - Hsia, Connie C W
PY - 2007/8
Y1 - 2007/8
N2 - We (42) previously reported differential regulation of hypoxia-inducible factors (HIF-1α, -2α, and -3α) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%. In three other animals, the prosthesis remained inflated. Three days following deflation, we observed significant elevation in the mRNA and nuclear protein levels of HIF-1α (∼60%) as well as activation of its transcriptional regulator, the serine/threonine protein kinase B (phospho-Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream targets, erythropoietin receptor (71-183%) as well as VEGF (33-58%) compared with the pre-PNX control lung from the same animal. The mRNA of HIF-2α, HIF-3α, and VEGF receptors did not change with acute deflation. We conclude that in vivo lung expansion by post-PNX deflation of space-occupying prosthesis elicits coordinated activation of HIF-1α signaling in adult lungs. This pathway could play an important role in mediating lung growth and remodeling during maturation and post-PNX compensation.
AB - We (42) previously reported differential regulation of hypoxia-inducible factors (HIF-1α, -2α, and -3α) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%. In three other animals, the prosthesis remained inflated. Three days following deflation, we observed significant elevation in the mRNA and nuclear protein levels of HIF-1α (∼60%) as well as activation of its transcriptional regulator, the serine/threonine protein kinase B (phospho-Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream targets, erythropoietin receptor (71-183%) as well as VEGF (33-58%) compared with the pre-PNX control lung from the same animal. The mRNA of HIF-2α, HIF-3α, and VEGF receptors did not change with acute deflation. We conclude that in vivo lung expansion by post-PNX deflation of space-occupying prosthesis elicits coordinated activation of HIF-1α signaling in adult lungs. This pathway could play an important role in mediating lung growth and remodeling during maturation and post-PNX compensation.
KW - Compensatory lung growth
KW - Dog
KW - Erythropoietin receptor
KW - Lung resection
KW - Lung volume
KW - Serine/threonine protein kinase B
KW - Vascular endothelial growth factor
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U2 - 10.1152/ajplung.00393.2006
DO - 10.1152/ajplung.00393.2006
M3 - Article
C2 - 17513452
AN - SCOPUS:34547613153
SN - 1040-0605
VL - 293
SP - L497-L504
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 2
ER -