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Feline Chronic Kidney Disease Is Associated with Upregulation of Transglutaminase 2: A Collagen Cross-Linking Enzyme

Sanchez-Lara, A C; Elliott, J; Syme, H M; Brown, C A; Haylor, J L


A C Sanchez-Lara

J Elliott

H M Syme

C A Brown

J L Haylor


Chronic kidney disease is a major cause of morbidity and mortality in cats. Transglutaminase 2 (TG2) is a calcium-dependent enzyme proposed to mediate tubulointerstitial fibrosis in the kidney by cross-linking collagen fibrils. Postmortem kidney tissue was obtained from primary renal azotemic (n = 10) and nonazotemic (n = 5) cats (14 domestic short hair, 1 Burmese; aged 9–23.7 years). Extracellular matrix protein deposition was determined by Masson’s trichrome staining and collagen immunofluorescence. Total kidney transglutaminase (TG) enzyme activity and TG2 protein were measured in tissue homogenates by putrescine incorporation and Western blotting. Extracellular TG enzyme activity and TG2 protein were determined in situ by immunofluorescence, quantified by multiphase image analysis. Results were compared using the unpaired Student’s t-test with Welch’s correction. Elevated plasma creatinine, urea, and phosphate concentrations were associated with tubulointerstitial fibrosis but not glomerular fibrosis. Kidney homogenates from azotemic cats showed a 3-fold higher total TG enzyme activity and TG2 protein compared with kidneys from nonazotemic cats. Immunofluorescent studies performed in situ confirmed a 3-fold higher extracellular TG enzyme activity and TG2 protein in cats with azotemia. Tubulointerstitial TG2 showed a positive linear correlation with both renal function and tubulointerstitial fibrosis. In conclusion, for cats with azotemia, both filtration failure and tubulointerstitial fibrosis were associated with the upregulation of TG2, a collagen cross-linking enzyme and the major isoform of transglutaminase in the kidney. TG2 may provide a new therapeutic target for drugs designed to slow the progression of feline chronic kidney disease.


Sanchez-Lara, A. C., Elliott, J., Syme, H. M., Brown, C. A., & Haylor, J. L. (2015). Feline Chronic Kidney Disease Is Associated with Upregulation of Transglutaminase 2: A Collagen Cross-Linking Enzyme. Veterinary Pathology, 52(3), 513-523.

Journal Article Type Article
Acceptance Date Mar 1, 2014
Publication Date May 1, 2015
Deposit Date Nov 11, 2014
Print ISSN 0300-9858
Publisher American College of Veterinary Pathologists
Peer Reviewed Peer Reviewed
Volume 52
Issue 3
Pages 513-523
Public URL
Additional Information Corporate Creators : Georgia, Sheffield