Abstract
Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries.
Highlights
Proper development of renal vasculature involves the coordination of several processes, including endothelial cell proliferation, migration, homotypic and heterotypic intercellular adhesion, and morphogenesis
Our results demonstrate that; 1) both Vascular endothelial-PTP (VE-PTP) and PTPμ are expressed in the endothelium of arterial, glomerular, and medullary vasculatures in developing and adult kidneys; 2) their expression increases as renal vascular development proceeds; 3) the expression of these receptortype tyrosine phosphatases (RPTPs) is highly limited in venous endothelium
The present study investigated for the first time the expression of two endothelial RPTPs, VE-PTP and PTPμ, in developing and mature renal vasculature
Summary
Proper development of renal vasculature involves the coordination of several processes, including endothelial cell proliferation, migration, homotypic and heterotypic intercellular adhesion, and morphogenesis. A body of studies has defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) and their activating ligands in promoting and coordinating renal vascular development, especially in glomerular microvascular development [1, 2]. These include VEGFs and VEGF receptors, angiopoietins and Tie receptors, and ephrins and Eph receptors [2,3,4]. A more recent study has shown that VE-PTP inhibition stabilizes endothelial junctions via Tie-2 even in the absence of VE-cadherin [13] These findings indicate an important role for VE-PTP to balance Tie activity and regulate vessel formation and stability. The extracellular ligands for VE-PTP remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
