RGD Reference Report - Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury. - Rat Genome Database

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Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury.

Authors: Wang, F  Zhang, G  Lu, Z  Geurts, AM  Usa, K  Jacob, HJ  Cowley, AW  Wang, N  Liang, M 
Citation: Wang F, etal., Kidney Int. 2015 Oct;88(4):796-803. doi: 10.1038/ki.2015.176. Epub 2015 Jun 24.
RGD ID: 11354006
Pubmed: PMID:26108065   (View Abstract at PubMed)
PMCID: PMC4589441   (View Article at PubMed Central)
DOI: DOI:10.1038/ki.2015.176   (Journal Full-text)

Antithrombin III, encoded by SerpinC1, is a major anti-coagulation molecule in vivo and has anti-inflammatory effects. We found that patients with low antithrombin III activities presented a higher risk of developing acute kidney injury after cardiac surgery. To study this further, we generated SerpinC1 heterozygous knockout rats and followed the development of acute kidney injury in a model of modest renal ischemia/reperfusion injury. Renal injury, assessed by serum creatinine and renal tubular injury scores after 24 h of reperfusion, was significantly exacerbated in SerpinC1(+/-) rats compared to wild-type littermates. Concomitantly, renal oxidative stress, tubular apoptosis, and macrophage infiltration following this injury were significantly aggravated in SerpinC1(+/-) rats. However, significant thrombosis was not found in the kidneys of any group of rats. Antithrombin III is reported to stimulate the production of prostaglandin I2, a known regulator of renal cortical blood flow, in addition to having anti-inflammatory effects and to protect against renal failure. Prostaglandin F1alpha, an assayable metabolite of prostaglandin I2, was increased in the kidneys of the wild-type rats at 3 h after reperfusion. The increase of prostaglandin F1alpha was significantly blunted in SerpinC1(+/-) rats, which preceded increased tubular injury and oxidative stress. Thus, our study found a novel role of SerpinC1 insufficiency in increasing the severity of renal ischemia/reperfusion injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute kidney failure  IEP 11354006associated with heart failure and protein:decreased activity:plasma:RGD 
acute kidney failure  ISOSERPINC1 (Homo sapiens)11354006; 11354006associated with heart failure and protein:decreased activity:plasma:RGD 
Kidney Reperfusion Injury  ISOSerpinc1 (Rattus norvegicus)11354006; 11354006 RGD 
Kidney Reperfusion Injury severityISOSerpinc1 (Rattus norvegicus)11354006; 11354006 RGD 
Kidney Reperfusion Injury  IMP 11354006; 11354006; 11354006 RGD 
Kidney Reperfusion Injury severityIMP 11354006 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased susceptibility to kidney reperfusion injury  IMP 11354006; 11354006; 11354006 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Serpinc1  (serpin family C member 1)
Serpinc1em2Mcwi  (serpin family C member 1; ZFN induced mutant 2, Medical College of Wisconsin)

Genes (Mus musculus)
Serpinc1  (serine (or cysteine) peptidase inhibitor, clade C (antithrombin), member 1)

Genes (Homo sapiens)
SERPINC1  (serpin family C member 1)


Additional Information