RGD Reference Report - Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice. - Rat Genome Database

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Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice.

Authors: Xu, ZE  Chen, Y  Huang, A  Varghese, Z  Moorhead, JF  Yan, F  Powis, SH  Li, Q  Ruan, XZ 
Citation: Xu ZE, etal., Am J Physiol Renal Physiol. 2011 Oct;301(4):F713-22. doi: 10.1152/ajprenal.00341.2010. Epub 2011 Jul 27.
RGD ID: 7241070
Pubmed: PMID:21795641   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00341.2010   (Journal Full-text)

Both lipids and inflammation play important roles in the progression of kidney disease. This study was designed to investigate whether inflammation exacerbates lipid accumulation via LDL receptors (LDLr), thereby causing renal injury in C57BL/6J mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE/CD36/scavenger receptor A triple KO mice. The mice were given a subcutaneous casein injection to induce inflammatory stress. After 14 wk, terminal blood samples were taken for renal function, lipid profiles, amyloid A (SAA), and IL-6 assays. Lipid accumulation in kidneys was visualized by oil red O staining. Fibrogenic molecule expression in kidneys was examined. There was a significant increase in serum SAA and IL-6 in the all casein-injected mice compared with respective controls. Casein injection reduced serum total cholesterol, LDL cholesterol, and HDL cholesterol and caused lipid accumulation in kidneys from three types of mice. The expression of LDLr and its regulatory proteins sterol-responsive element-binding protein (SREBP) 2 and SREBP cleavage-activating protein (SCAP) were upregulated in inflamed mice compared with controls. Casein injection induced renal fibrosis accompanied by increased expression of fibrogenic molecules in the triple KO mice. These data imply that inflammation exacerbates lipid accumulation in the kidney by diverting lipid from the plasma to the kidney via the SCAP-SREBP2-LDLr pathway and causing renal injury. Low blood cholesterol levels, resulting from inflammation, may be associated with high risk for chronic renal fibrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kidney disease  ISOLdlr (Mus musculus)7241070; 7241070 RGD 
kidney disease  IEP 7241070 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ldlr  (low density lipoprotein receptor)

Genes (Mus musculus)
Ldlr  (low density lipoprotein receptor)

Genes (Homo sapiens)
LDLR  (low density lipoprotein receptor)


Additional Information