Nephrin and endothelial injury.
OBJECTIVE
Nephrin, the main structural protein of the slit diaphragm, is expressed on the surface of glomerular podocytes and is critical in maintaining permselectivity and preventing proteinuria. This review focuses on the fate of nephrin in the context of endothelial injury and gives an update on the recent progress in understanding the pathomechanisms that lead to proteinuria.


RESULTS
The following conditions of endothelial injury were found to induce loss of nephrin.(1) Preeclampsia, in which the associated proteinuria is induced by the soluble variant of vascular endothelial growth factor, which stimulates production of endothelin 1 (ET1) in endothelial cells. ET1 in turn triggers nephrin shedding from podocytes.(2) Hypertension, in which increased levels of angiotensin II induce podocyte apoptosis and reduce nephrin expression, leading to proteinuria in rats.(3) Diabetes and high fat diet, which lead to a significant increase in inflammatory molecules and cytokines, including MCP-1, which induces changes in podocyte cytoskeleton and nephrin loss.


CONCLUSIONS
Recent results showed that damage to endothelial cells may alter endothelial-podocyte interaction and induces nephrin loss, a main cause of proteinuria.
Hauser
Peter V
PV
Department of Internal Medicine and Center for Molecular Biotechnology, University of Torino, Torino, Italy.
Collino
Federica
F
Bussolati
Benedetta
B
Camussi
Giovanni
G
D000818:Animals; D003928:Diabetic Nephropathies / Q000473:pathology; D004041:Dietary Fats; D042783:Endothelial Cells / Q000473:pathology; D004727:Endothelium / Q000473:pathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D050199:Podocytes / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology
D004041:Dietary Fats; D008565:Membrane Proteins; C113267:nephrin