RGD Reference Report - Effect of losartan on the mRNA expressions of MT3-MMP and TIMP-2 in diabetic kidneys. - Rat Genome Database

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Effect of losartan on the mRNA expressions of MT3-MMP and TIMP-2 in diabetic kidneys.

Authors: Ding, HL  Xu, MT  Guo, Y  Chen, L  Zhang, SL  Li, F  Fu, ZZ 
Citation: Ding HL, etal., Rev Diabet Stud. 2005 Winter;2(4):216-20. Epub 2006 Feb 10.
RGD ID: 2290407
Pubmed: PMID:17491697   (View Abstract at PubMed)
PMCID: PMC1783568   (View Article at PubMed Central)
DOI: DOI:10.1900/RDS.2005.2.216   (Journal Full-text)

BACKGROUND AND OBJECTIVES: The renin-angiotensin system plays a critical role in circulatory homoeostasis. Evidence has emerged that suggests a pathologic role for angiotensin II in patients with kidney disease. Losartan is an antagonist of angiotensin II and blocks the angiotensin II type-1 receptor. Thus it may reduce proteinuria and delay the progression of renal disease in diabetic nephropathy. We investigated the effects of losartan on the mRNA expressions of membrane-type3 matrix metalloproteinases (MT3-MMP) and the tissue inhibitor of metalloproteinase-2 (TIMP-2) in diabetic kidneys in order to evaluate degradation and remodeling of the extracellular matrix. METHODS: Male Wistar rats were divided into 3 groups. Group A was the control group containing healthy rats (n = 11), group B comprised diabetic rats without any therapy (n = 11), and group C consisted of diabetic rats treated with losartan (n = 9). 24-hr urine samples were collected in order to measure urinary albumin excretion (UAE). After a period of 18 weeks, the kidneys were extracted from all rats in order to measure the mRNA expressions of MT3-MMP, TIMP-2 and transforming growth factor-beta1 (TGF-beta1) by RT-PCR. We also examined the glomerular basement membrane thickening and the mesangial matrix (MM) density (MM area/mesangial area). RESULTS: The expression of renal MT3-MMP mRNA in group B (1.37 +/- 0.96) was significantly higher than that in group A (0.75 +/- 0.34, p < 0.05), but also significantly higher than in group C (0.75 +/- 0.30, p < 0.05). Similarly, the mRNA expression of renal TIMP-2 in group B (0.73 +/- 0.37) was significantly increased compared to that in group A (0.32 +/- 0.19, p < 0.05), but also higher than in group C (0.34 +/- 0.17, p < 0.05). In addition, subjects in group B showed abundant TGF-beta1 mRNA expression and UAE compared to groups A and C, as well as significantly higher glomerular basement membrane thickening and MM density (all p < 0.05). CONCLUSIONS: We conclude that MT3-MMP and TIMP-2 production in the renal cortex of diabetic kidneys is increased. Losartan can prevent the development of diabetic nephropathy by decreasing MT3-MMP and TIMP2 production in diabetic kidneys.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOTimp2 (Rattus norvegicus)2290407; 2290407mRNA:increased expression:kidneyRGD 
Diabetic Nephropathies  IEP 2290407mRNA:increased expression:kidneyRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 2290407 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Timp2  (TIMP metallopeptidase inhibitor 2)

Genes (Mus musculus)
Timp2  (tissue inhibitor of metalloproteinase 2)

Genes (Homo sapiens)
TIMP2  (TIMP metallopeptidase inhibitor 2)


Additional Information