Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

Kristin M. Shields; Evgeniy Panzhinskiy; Nana Burns; W. Michael Zawada; Mita Das

doi:10.1016/j.ajpath.2010.11.025

Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

Kristin M. Shields, Evgeniy Panzhinskiy, Nana Burns, W. Michael Zawada, Mita Das^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Web of Science)

Abstract

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 (

Original language	English
Pages (from-to)	98-109
Journal	American Journal of Pathology
Volume	178
Issue number	1
DOIs	https://doi.org/10.1016/j.ajpath.2010.11.025
Publication status	Published - Jan 2011

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@article{5f9974656edb498283cae02eb8159783,

title = "Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung",

abstract = "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 (",

author = "Shields, {Kristin M.} and Evgeniy Panzhinskiy and Nana Burns and Zawada, {W. Michael} and Mita Das",

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Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung. / Shields, Kristin M.; Panzhinskiy, Evgeniy; Burns, Nana et al.
In: American Journal of Pathology, Vol. 178, No. 1, 01.2011, p. 98-109.

Research output: Contribution to journal › Article › Academic › peer-review

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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 (

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