Work

Polycystin Signaling Is Required for Directed Endothelial Cell Migration and Lymphatic Development

Year: 2014

Type: article

Abstract: Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1) and PKD2 (polycystin-2). Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development.

Source: Cell Reports

DOI: 10.1016/j.celrep.2014.03.064

Authors: Patricia Outeda, David L. Huso, Steven A. Fisher, Marc K. Halushka, Hyunho Kim, Feng Qian, Gregory G. Germino, Terry Watnick

Institutions: University of Maryland, Baltimore, Johns Hopkins University, Johns Hopkins Medicine, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

Language: English

Topic: Lymphatic System and Diseases

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620

Funders: National Institutes of Health, U.S. Public Health Service, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, NIH Clinical Center

Awards: Comprehensive Analysis of Polycystin Related Endothelial Cell Signaling Pathways, Hopkins Digestive Diseases Basic & Translational Research Core Center, G2795649559, Tissue Hypoxia in Cardiac Morphogenesis, Baltimore Polycystic Kidney Disease Research and Clinical Core Center, Ion Channel Function and Regulation of the Polycystin-1/2 Complex in Kidney Physiology and Polycystic Kidney Disease, Novel Approach to the Molecular Genetics of PKD1, PKD1-Fibrillin Interactions and TFG-b Signaling Pathways, The Proteolytic Cleavage of Polycystin-1: How and Why, The role of PKD proteins in regulating tubular morphology

OpenAlex ID: W1991969354

FWCI: 4.37

Cites: 34

Cited by: 82

Related to: 10