Sterol regulatory element-binding proteins, liver X receptor, ABCA1 transporter, CD36, scavenger receptors A1 and B1 in nephrotic kidney.
BACKGROUND
Accumulation of lipid in the kidney has been shown to promote renal disease. Heavy glomerular proteinuria (nephrotic syndrome) is associated with hyperlipidemia, lipiduria, and progressive kidney disease. Glomerular and tubular epithelial cells in the nephrotic kidney are exposed to large quantities of lipids bound to the filtered proteins whose uptake can raise cellular lipids. Cellular lipid homeostasis is regulated by the influx, synthesis and efflux of lipids.


METHODS
We studied the expression of factors involved in lipid metabolism in the kidneys of nephrotic and control rats.


RESULTS
The nephrotic rats showed heavy proteinuria, hypercholesterolemia, increased kidney tissue cholesterol, marked activation (nuclear translocation) of SREBP-2 (master regulator of cholesterol synthesis), significant upregulations of CD36 and SRA-1 (key receptors for uptake of fatty acids and oxidized LDL) and ACAT1 (enzyme catalyzing intracellular esterification, hence trapping of cholesterol), but no significant change in either ABCA1 (mediator of cholesterol/phospholipid efflux) or its regulator, liver X receptor.


CONCLUSIONS
Proteinuria results in accumulation of cholesterol in the kidney. This is associated with upregulation of SRA-1, CD36 and ACAT1 and activation of SREBP-2 which can collectively raise tissue cholesterol and promote renal injury by facilitating the influx, synthesis and retention of cholesterol in the nephrotic kidney.
Kim
Hyun Ju
HJ
Division of Nephrology and Hypertension, University of California, Irvine, CA 92868, USA.
Vaziri
Nosratola D
ND
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D051779:Sterol Regulatory Element Binding Proteins; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase