Diaphragmed fenestrae in the glomerular endothelium versus nondiaphragmed fenestrae in the hepatic endothelium

Abstract

To the Editor: In a recent issue of Kidney International, Ballermann1.Ballermann B. Glomerular endothelial cell differentiation.Kidney Int. 2005; 67: 1668-1671Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar discussed the development of diaphragmed fenestrae in glomerular endothelial cells. Major similarities exist between the hepatic and the glomerular endothelium regarding the process of fenestrae formation; intriguingly, an analogous controversy about the origin of fenestrae exists in both the hepatology and nephrology fields2.Braet F. How molecular microscopy revealed new insights in the dynamics of hepatic endothelial fenestrae in the past decade.Liver Int. 2004; 24: 532-539Crossref PubMed Scopus (26) Google Scholar. Hepatic endothelial fenestrae are dynamic structures that act as a sieving barrier to control the extensive exchange of material between the blood and the liver parenchyma. These membrane-bound pores lack a diaphragm and a basal lamina is also absent (Fig. 1A and B, arrows), in contrast to fenestrae described in the kidney, pancreas, and brain. Their biological relevance in various diseases has been widely acknowledged3.Braet F. Wisse E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: A review.Comparative Hepatology. 2002; 1: 1Crossref PubMed Scopus (485) Google Scholar. Evidence that VEGF-induced diaphragmed fenestrae are derived from fused caveolae has recently been accumulating. It has been postulated that a similar mechanism is used in the formation of hepatic fenestrae. Conversely, actin disruption in hepatic endothelial cells produces an increase in the number of fenestrae by using a distinct structure that appears to serve as a fenestrae-forming center Fig. 1C4.Braet F. Spector I. De Zanger R. Wisse E. A novel structure involved in the formation of liver endothelial cell fenestrae revealed using the actin inhibitor misakinolide.Proc Natl Acad Sci USA. 1998; 95: 13635-13640Crossref PubMed Scopus (61) Google Scholar. Furthermore, it is important to emphasize the contradictions in the data reported about the origin of fenestrae in kidney, pancreas, and in the liver. For example, some data either clearly or indirectly indicate a possible relationship between caveolae, vesiculo-vacuolar organelles, and (diaphragmed) fenestrae; others suggest the opposite (reviewed in2.Braet F. How molecular microscopy revealed new insights in the dynamics of hepatic endothelial fenestrae in the past decade.Liver Int. 2004; 24: 532-539Crossref PubMed Scopus (26) Google Scholar). Therefore, until this controversy is settled, no firm conclusions can be drawn, and stating that fenestrae, whether diaphragmed or not, correspond to fused and interconnected caveolae should be viewed with caution and remains as an emerging research topic.