RGD Reference Report - Sterol Regulatory Element-Binding Proteins, Liver X Receptor, ABCA1 Transporter, CD36, Scavenger Receptors A1 and B1 in Nephrotic Kidney. - Rat Genome Database

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Sterol Regulatory Element-Binding Proteins, Liver X Receptor, ABCA1 Transporter, CD36, Scavenger Receptors A1 and B1 in Nephrotic Kidney.

Authors: Kim, HJ  Vaziri, ND 
Citation: Kim HJ and Vaziri ND, Am J Nephrol. 2009 Jan 16;29(6):607-614.
RGD ID: 2307223
Pubmed: PMID:19147991   (View Abstract at PubMed)
DOI: DOI:10.1159/000193631   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nephrosis  ISOCd36 (Rattus norvegicus)2307223; 2307223 RGD 
nephrosis  IEP 2307223 RGD 
nephrosis  ISOSrebf2 (Rattus norvegicus)2307223; 2307223protein:altered localization:nucleusRGD 
nephrosis  IEP 2307223protein:altered localization:nucleusRGD 
nephrotic syndrome  ISOAcat1 (Rattus norvegicus)2307223; 2307223protein:increased expression:kidney (rat)RGD 
nephrotic syndrome  IEP 2307223protein:increased expression:kidney (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acat1  (acetyl-CoA acetyltransferase 1)
Cd36  (CD36 molecule)
Srebf2  (sterol regulatory element binding transcription factor 2)

Genes (Mus musculus)
Acat1  (acetyl-Coenzyme A acetyltransferase 1)
Cd36  (CD36 molecule)
Srebf2  (sterol regulatory element binding factor 2)

Genes (Homo sapiens)
ACAT1  (acetyl-CoA acetyltransferase 1)
CD36  (CD36 molecule (CD36 blood group))
SREBF2  (sterol regulatory element binding transcription factor 2)


Additional Information