Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M405254200 on June 14, 2004

J. Biol. Chem., Vol. 279, Issue 35, 37124-37132, August 27, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/35/37124    most recent
M405254200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reynolds, P. R.
Right arrow Articles by Whitsett, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reynolds, P. R.
Right arrow Articles by Whitsett, J. A.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Midkine Is Regulated by Hypoxia and Causes Pulmonary Vascular Remodeling*

Paul R. Reynolds{ddagger}, Michael L. Mucenski{ddagger}, Timothy D. Le Cras{ddagger}, William C. Nichols§, and Jeffrey A. Whitsett{ddagger}

From the {ddagger}Divisions of Pulmonary Biology and §Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039

Midkine (MK) is expressed in a precise temporal-spatial pattern during lung morphogenesis; however, its role in pulmonary homeostasis is unknown. Increased MK staining and mRNA expression were observed in the lungs of hypoxia-susceptible CAST/eiJ mice during hypoxia. MK expression was induced by hypoxia in cell lines in vitro. Because the transcription factor hypoxiainducible factor-1{alpha} (HIF-1{alpha}) modulates cellular responses to hypoxia, we tested whether increased expression of MK in the lung was mediated by HIF-1{alpha}. HIF-1{alpha} enhanced the transcription of MK, acting on HIF-1{alpha} regulatory elements located in the MK gene promoter. Site-directed mutagenesis of the 3' HIF response element in the MK promoter blocked the stimulatory effects of HIF-1{alpha}. To directly assess the role of MK on lung morphogenesis, transgenic mice were generated in which MK was expressed in the respiratory epithelial cells of the developing lung. MK increased muscularization of small pulmonary arteries, increasing {alpha}-smooth muscle actin and caldesmon staining and the expression of myocardin. MK directly enhanced the expression of myocardin and the smooth muscle-specific genes {alpha}-smooth muscle actin, calponin, and SM-22 in vascular smooth muscle precursor cells. Expression of MK in the respiratory epithelium is regulated by hypoxia and HIF-1{alpha}. These data provide a model wherein the respiratory epithelium responds to hypoxia via HIF-1{alpha}-dependent regulation of MK, enhancing myocardin expression to influence pulmonary vascular gene expression.


Received for publication, May 11, 2004 , and in revised form, June 8, 2004.

* This work was supported by National Institutes of Health Grants HL38859, HL75770, and HL56387 (Pathobiology of Lung Development) (to J. A. W.), HL72894 (to T. D. L. C.), HL72058 (to W. C. N.), and HD07463 (to P. R. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Tel.: 513-636-4830; Fax: 513-636-7868; E-mail: jeff.whitsett{at}cchmc.org.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Zhou, S. Negash, J. Liu, and J. U. Raj
Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of cGMP-dependent protein kinase and myocardin
Am J Physiol Lung Cell Mol Physiol, May 1, 2009; 296(5): L780 - L789.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
H. Takenaka, M. Horiba, H. Ishiguro, A. Sumida, M. Hojo, A. Usui, T. Akita, S. Sakuma, Y. Ueda, I. Kodama, et al.
Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction
Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H462 - H469.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. R. Reynolds, S. D. Kasteler, M. G. Cosio, A. Sturrock, T. Huecksteadt, and J. R. Hoidal
RAGE: developmental expression and positive feedback regulation by Egr-1 during cigarette smoke exposure in pulmonary epithelial cells
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1094 - L1101.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. D. Hardie, C. Davidson, M. Ikegami, G. D. Leikauf, T. D. Le Cras, A. Prestridge, J. A. Whitsett, and T. R. Korfhagen
EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-{alpha}-induced pulmonary fibrosis
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1217 - L1225.
[Abstract] [Full Text] [PDF]


Home page
Proc Am Thorac SocHome page
K. R. Badri, Y. Zhou, and L. Schuger
Embryological Origin of Airway Smooth Muscle
Proceedings of the ATS, January 1, 2008; 5(1): 4 - 10.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
S. Chen, G. Bu, Y. Takei, K. Sakamoto, S. Ikematsu, T. Muramatsu, and K. Kadomatsu
Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells
J. Cell Sci., November 15, 2007; 120(22): 4009 - 4015.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Cell Mol. Bio.Home page
W. D. Hardie, T. R. Korfhagen, M. A. Sartor, A. Prestridge, M. Medvedovic, T. D. Le Cras, M. Ikegami, S. C. Wesselkamper, C. Davidson, M. Dietsch, et al.
Genomic Profile of Matrix and Vasculature Remodeling in TGF-{alpha} Induced Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 309 - 321.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. L. Kramer, G. H. Deutsch, M. A. Sartor, W. D. Hardie, M. Ikegami, T. R. Korfhagen, and T. D. Le Cras
Perinatal increases in TGF-{alpha} disrupt the saccular phase of lung morphogenesis and cause remodeling: microarray analysis
Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L314 - L327.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
N. Chow, R. D. Bell, R. Deane, J. W. Streb, J. Chen, A. Brooks, W. Van Nostrand, J. M. Miano, and B. V. Zlokovic
Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype
PNAS, January 16, 2007; 104(3): 823 - 828.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Cell Mol. Bio.Home page
P. R. Reynolds, M. G. Cosio, and J. R. Hoidal
Cigarette Smoke-Induced Egr-1 Upregulates Proinflammatory Cytokines in Pulmonary Epithelial Cells
Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 314 - 319.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Hinton, L. Mellow, A. J. Halayko, A. Gutsol, and S. Dakshinamurti
Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L375 - L384.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
I.-M. Kim, S. Ramakrishna, G. A. Gusarova, H. M. Yoder, R. H. Costa, and V. V. Kalinichenko
The Forkhead Box M1 Transcription Factor Is Essential for Embryonic Development of Pulmonary Vasculature
J. Biol. Chem., June 10, 2005; 280(23): 22278 - 22286.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
G. Steele-Perkins, C. Plachez, K. G. Butz, G. Yang, C. J. Bachurski, S. L. Kinsman, E. D. Litwack, L. J. Richards, and R. M. Gronostajski
The Transcription Factor Gene Nfib Is Essential for both Lung Maturation and Brain Development
Mol. Cell. Biol., January 15, 2005; 25(2): 685 - 698.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement