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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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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. |
format | Online Article Text |
id | pubmed-4131109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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