RGD Reference Report - Arginase-2 mediates diabetic renal injury. - Rat Genome Database

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Arginase-2 mediates diabetic renal injury.

Authors: Morris SM, JR  Gao, T  Cooper, TK  Kepka-Lenhart, D  Awad, AS 
Citation: Morris SM Jr, etal., Diabetes. 2011 Nov;60(11):3015-22. Epub 2011 Sep 16.
RGD ID: 6902923
Pubmed: PMID:21926276   (View Abstract at PubMed)
PMCID: PMC3198072   (View Article at PubMed Central)
DOI: DOI:10.2337/db11-0901   (Journal Full-text)

OBJECTIVE: To determine 1) whether renal arginase activity or expression is increased in diabetes and 2) whether arginase plays a role in development of diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS: The impact of arginase activity and expression on renal damage was evaluated in spontaneously diabetic Ins2(Akita) mice and in streptozotocin (STZ)-induced diabetic Dilute Brown Agouti (DBA) and arginase-2-deficient mice (Arg2(-/-)). RESULTS: Pharmacological blockade or genetic deficiency of arginase-2 conferred kidney protection in Ins2(Akita) mice or STZ-induced diabetic renal injury. Blocking arginases using S-(2-boronoethyl)-L-cysteine for 9 weeks in Ins2(Akita) mice or 6 weeks in STZ-induced diabetic DBA mice significantly attenuated albuminuria, the increase in blood urea nitrogen, histopathological changes, and kidney macrophage recruitment compared with vehicle-treated Ins2(Akita) mice. Furthermore, kidney arginase-2 expression increased in Ins2(Akita) mice compared with control. In contrast, arginase-1 expression was undetectable in kidneys under normal or diabetes conditions. Arg2(-/-) mice mimicked arginase blockade by reducing albuminuria after 6 and 18 weeks of STZ-induced diabetes. In wild-type mice, kidney arginase activity increased significantly after 6 and 18 weeks of STZ-induced diabetes but remained very low in STZ-diabetic Arg2(-/-) mice. The increase in kidney arginase activity was associated with a reduction in renal medullary blood flow in wild-type mice after 6 weeks of STZ-induced diabetes, an effect significantly attenuated in diabetic Arg2(-/-) mice. CONCLUSIONS: These findings indicate that arginase-2 plays a major role in induction of diabetic renal injury and that blocking arginase-2 activity or expression could be a novel therapeutic approach for treatment of DN.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOArg2 (Mus musculus)6902923; 6902923 RGD 
Diabetic Nephropathies  IMP 6902923 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arg2  (arginase 2)

Genes (Mus musculus)
Arg2  (arginase type II)

Genes (Homo sapiens)
ARG2  (arginase 2)


Additional Information