RGD Reference Report - Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys. - Rat Genome Database

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Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys.

Authors: Shimoda, N  Fukazawa, N  Nonomura, K  Fairchild, RL 
Citation: Shimoda N, etal., Am J Pathol. 2007 Mar;170(3):930-40.
RGD ID: 7242055
Pubmed: PMID:17322378   (View Abstract at PubMed)
PMCID: PMC1864870   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.060486   (Journal Full-text)

Neutrophil activation to release granules containing proteases and other enzymes is a primary cause of tissue damage during ischemia/reperfusion injury. Because the contribution of specific granule enzymes to this injury remains poorly defined, the role of cathepsin G in renal ischemia/reperfusion injury was tested. Bilateral renal ischemia led to the expiration of 64% of wild-type mice within 4 days of reperfusion, whereas all cathepsin G-deficient mice survived. Serum creatinine increased to similar levels at 24 hours after reperfusion and then decreased to background in both groups of mice. Ischemic kidneys from both groups had similar levels of neutrophil infiltration and of CXCL1, CXCL2, and myeloperoxidase protein 9 hours after reperfusion, but at 24 hours, these acute inflammatory response components were decreased more than 50% in kidneys from cathepsin G-deficient versus wild-type mice. Ischemic kidneys from surviving wild-type mice had severe tubular necrosis and tubular cell apoptosis 24 hours after reperfusion with subsequent development of fibrosis 30 days later. In contrast, ischemic kidneys from cathepsin G-deficient mice had a 70% decrease in tubular cell apoptosis with little detectable collagen deposition. These data identify cathepsin G as a critical component sustaining neutrophil-mediated acute tissue pathology and subsequent fibrosis after renal ischemia/reperfusion injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reperfusion Injury  ISOCtsg (Mus musculus)7242055; 7242055 RGD 
Reperfusion Injury  IMP 7242055 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctsg  (cathepsin G)

Genes (Mus musculus)
Ctsg  (cathepsin G)

Genes (Homo sapiens)
CTSG  (cathepsin G)


Additional Information