Page Banner

United States Department of Agriculture

Agricultural Research Service

Title: Pv-1 Is Negatively Regulated by Vegf in the Lung of Cav-1, But Not Cav-2, Null Mice

Authors
item Hnasko, Robert
item Ben-Jonathan, Nira - UNIV OF CINCINATI
item Lisanti, Michael - THOMAS JEFFERSON UNIV

Submitted to: Cell Cycle
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2006
Publication Date: September 1, 2006
Citation: Hnasko, R.M., Philippe, F.G., Ben-Jonathan, N., Lisanti, M.P. 2006. Pv-1 is negatively regulated by vegf in the lung of cav-1, but not cav-2, null mice. Cell Cycle 5(17):2012-20.

Interpretive Summary: Blood vessels provide a barrier of entry of substances from the blood into tissues and organs. This barrier often impedes the delivery of pharmacological agents to target tissues and limits there therapeutic utility. Moreover, blood vessels in different tissues have distinct properties that allow for the selective passage of agents with both beneficial and deleterious effect. Understanding the nature of selective blood vessel permeability and how this process is regulated is essential to the therapeutic utility of drugs aimed at the treatment of disease. In this report we identify a specific blood vessel protein (PV-1) in the lung that is negatively regulated in transgenic mice that lack cellular caveolae. These animals have abnormal blood vessels with altered permeability. We show that the pharmacological inhibition vascular growth factor receptors (VEGF-R2) positively upregulate the PV-1 protein. These data show that the loss of cell caveolae in lung blood vessels downregulates the PV-1 protein which may in turn contribute to their dysregulation and alteration permeability.

Technical Abstract: An N-glycosylated 60-kDa PV-1 protein that binds heparin was detected in mouse lung from a single mRNA transcript. In the absence of disulfide bond reduction PV-1 is detected as a dimer or large molecular weight oligomer. In the lung of Cav-1, but not Cav-2, null mice the amount of PV-1 protein is diminished, with no detectable change in mRNA level. PV-1 does not fractionate with caveolae on a sucrose density gradient, but the Cav-1 protein is detected in fractions following immunoprecipitation with PV-1 antibodies. Both PV-1 and Cav-1 localize to alveolar endothelial cells, but PV-1 is concentrated at the abluminal and Cav-1 at the luminal cell surface with minimal co-localization. In the Cav-1 null, PV-1 is nearly undetectable in endothelial cells, but remains unchanged in pneumocytes and bronchial epithelial cells. Injection of a VEGF-R2 inhibitor increased PV-1 protein in lung of Cav-1 null, but not Cav-2 or wild-type mice. These data indicate that the PV-1 protein is negatively regulated in pulmonary endothelial cells by VEGF-R2 signaling.

Last Modified: 9/2/2014
Footer Content Back to Top of Page