RGD Reference Report - Involvement of glomerular SREBP-1c in diabetic nephropathy. - Rat Genome Database

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Involvement of glomerular SREBP-1c in diabetic nephropathy.

Authors: Ishigaki, N  Yamamoto, T  Shimizu, Y  Kobayashi, K  Yatoh, S  Sone, H  Takahashi, A  Suzuki, H  Yamagata, K  Yamada, N  Shimano, H 
Citation: Ishigaki N, etal., Biochem Biophys Res Commun. 2007 Dec 21;364(3):502-8. Epub 2007 Oct 16.
RGD ID: 2308811
Pubmed: PMID:17961514   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2007.10.038   (Journal Full-text)

The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGFbeta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47phox, p67phox, and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-1c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MES13 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOSrebf1 (Mus musculus)2308811; 2308811associated with Diabetes Mellitus and ExperimentalRGD 
Diabetic Nephropathies  IMP 2308811 RGD 
Diabetic Nephropathies  ISOSREBF1 (Homo sapiens)2308811; 2308811 RGD 
Diabetic Nephropathies  IAGP 2308811associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Srebf1  (sterol regulatory element binding transcription factor 1)

Genes (Mus musculus)
Srebf1  (sterol regulatory element binding transcription factor 1)

Genes (Homo sapiens)
SREBF1  (sterol regulatory element binding transcription factor 1)

Objects referenced in this article
Gene Srebf1_v2 sterol regulatory element binding factor 1, variant 2 Rattus norvegicus

Additional Information