TY - JOUR
T1 - Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung
AU - Shields, Kristin M.
AU - Panzhinskiy, Evgeniy
AU - Burns, Nana
AU - Zawada, W. Michael
AU - Das, Mita
PY - 2011/1
Y1 - 2011/1
N2 - Although mitogen-activated protein kinase phosphatase-1 (MKP-1) is a key deactivator of MAP kinases, known effectors of lung vessel formation, whether it plays a role in the expression of proangiogenic vascular endothelial growth factor (VEGF) in hypoxic lung is unknown. We therefore hypothesized that MKP-1 is a crucial modulator of hypoxia-stimulated vessel development by regulating lung VEGF levels. Wild-type MKP-1(+/+), heterozygous MKP-1(+/-), and deficient MKP-1(-/-) mice were exposed to sea level (SL), Denver altitude (DA) (1609 m [5280 feet]), and severe high altitude (HYP) (?5182 m [?17,000 feet]) for 6 weeks. Hypoxia enhanced phosphorylation of p38 MAP kinase, a substrate of MKP-1, as well as ? smooth muscle actin (?SMA) expression in vessels, respiratory epithelium, and interstitium of phosphatase-deficient lung. ?SMA-positive vessel (
AB - Although mitogen-activated protein kinase phosphatase-1 (MKP-1) is a key deactivator of MAP kinases, known effectors of lung vessel formation, whether it plays a role in the expression of proangiogenic vascular endothelial growth factor (VEGF) in hypoxic lung is unknown. We therefore hypothesized that MKP-1 is a crucial modulator of hypoxia-stimulated vessel development by regulating lung VEGF levels. Wild-type MKP-1(+/+), heterozygous MKP-1(+/-), and deficient MKP-1(-/-) mice were exposed to sea level (SL), Denver altitude (DA) (1609 m [5280 feet]), and severe high altitude (HYP) (?5182 m [?17,000 feet]) for 6 weeks. Hypoxia enhanced phosphorylation of p38 MAP kinase, a substrate of MKP-1, as well as ? smooth muscle actin (?SMA) expression in vessels, respiratory epithelium, and interstitium of phosphatase-deficient lung. ?SMA-positive vessel (
U2 - 10.1016/j.ajpath.2010.11.025
DO - 10.1016/j.ajpath.2010.11.025
M3 - Article
C2 - 21224048
SN - 0002-9440
VL - 178
SP - 98
EP - 109
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -