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Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy

Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft ne...

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Autores principales: Shrestha, Badri, Butt, Imran, Da Silva, Michelle, Sanchez-Lara, Armando, Wagner, Bart, Raftery, Andrew, Johnson, Timothy, Haylor, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131109/
https://www.ncbi.nlm.nih.gov/pubmed/25143942
http://dx.doi.org/10.1155/2014/651608
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author Shrestha, Badri
Butt, Imran
Da Silva, Michelle
Sanchez-Lara, Armando
Wagner, Bart
Raftery, Andrew
Johnson, Timothy
Haylor, John
author_facet Shrestha, Badri
Butt, Imran
Da Silva, Michelle
Sanchez-Lara, Armando
Wagner, Bart
Raftery, Andrew
Johnson, Timothy
Haylor, John
author_sort Shrestha, Badri
collection PubMed
description Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 ± 17.61 versus 2.11 ± 0.17, P < 0.001; interstitium: 13.72 ± 1.62 versus 3.19 ± 0.44, P < 0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 ± 2.71 versus 1.98 ± 0.37, P < 0.01; interstitium: 37.96 ± 17.06 versus 0.42 ± 0.11, P < 0.05), TG2 enzyme activity (1.09 ± 0.13 versus 0.41 ± 0.03 nmol/h/mg protein, P < 0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 ± 198.4 nmol/24 h versus 57.2 ± 4.1 nmol/24 h, P < 0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN.
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spelling pubmed-41311092014-08-20 Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy Shrestha, Badri Butt, Imran Da Silva, Michelle Sanchez-Lara, Armando Wagner, Bart Raftery, Andrew Johnson, Timothy Haylor, John Biomed Res Int Research Article Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 ± 17.61 versus 2.11 ± 0.17, P < 0.001; interstitium: 13.72 ± 1.62 versus 3.19 ± 0.44, P < 0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 ± 2.71 versus 1.98 ± 0.37, P < 0.01; interstitium: 37.96 ± 17.06 versus 0.42 ± 0.11, P < 0.05), TG2 enzyme activity (1.09 ± 0.13 versus 0.41 ± 0.03 nmol/h/mg protein, P < 0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 ± 198.4 nmol/24 h versus 57.2 ± 4.1 nmol/24 h, P < 0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN. Hindawi Publishing Corporation 2014 2014-07-21 /pmc/articles/PMC4131109/ /pubmed/25143942 http://dx.doi.org/10.1155/2014/651608 Text en Copyright © 2014 Badri Shrestha et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Shrestha, Badri
Butt, Imran
Da Silva, Michelle
Sanchez-Lara, Armando
Wagner, Bart
Raftery, Andrew
Johnson, Timothy
Haylor, John
Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title_full Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title_fullStr Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title_full_unstemmed Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title_short Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy
title_sort upregulation of transglutaminase and ε (γ-glutamyl)-lysine in the fisher-lewis rat model of chronic allograft nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131109/
https://www.ncbi.nlm.nih.gov/pubmed/25143942
http://dx.doi.org/10.1155/2014/651608
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