BACKGROUND: Chronic allograft nephropathy, now more specifically termed interstitial fibrosis and tubular atrophy without evidence of any specific aetiology (IF/TA), is still an important cause of late graft loss. There is no effective therapy for IF/TA, in part due to the disease's multifactorial nature and its incompletely understood pathogenesis. METHODS: We used a differential in-gel electrophoresis and mass spectrometry technique to study IF/TA in a renal transplantation model. Dark Agouti (DA) kidneys were allogeneically transplanted to Wistar-Furth (DA-WF, aTX) rats. Syngeneic grafts (DA-DA, sTX) served as controls. Nine weeks after transplantation, blood pressure, renal function and electrolytes were studied, in addition to real-time PCR, western blot analysis, histology and immunohistochemistry. RESULTS: In contrast to sTX, the aTX developed IF/TA-dependent renal damage. Ten differentially regulated proteins were identified by 2D gel analysis and mass spectrometry, whereupon five proteins are mainly related to oxidative stress (aldo-keto reductase, peroxiredoxin-1, NAD(+)-dependent isocitrate dehydrogenase, iron-responsive element-binding protein-1 and serum albumin), two participate in cytoskeleton organization (l-plastin and ezrin) and three are assigned to metabolic functions (creatine kinase, ornithine aminotransferase and fructose-1,6-bisphosphatase). CONCLUSION: The proteins related to IF/TA and involved in oxidative stress, cytoskeleton organization and metabolic functions may correspond with novel therapeutic targets.
BACKGROUND: Chronic allograft nephropathy, now more specifically termed interstitial fibrosis and tubular atrophy without evidence of any specific aetiology (IF/TA), is still an important cause of late graft loss. There is no effective therapy for IF/TA, in part due to the disease's multifactorial nature and its incompletely understood pathogenesis. METHODS: We used a differential in-gel electrophoresis and mass spectrometry technique to study IF/TA in a renal transplantation model. Dark Agouti (DA) kidneys were allogeneically transplanted to Wistar-Furth (DA-WF, aTX) rats. Syngeneic grafts (DA-DA, sTX) served as controls. Nine weeks after transplantation, blood pressure, renal function and electrolytes were studied, in addition to real-time PCR, western blot analysis, histology and immunohistochemistry. RESULTS: In contrast to sTX, the aTX developed IF/TA-dependent renal damage. Ten differentially regulated proteins were identified by 2D gel analysis and mass spectrometry, whereupon five proteins are mainly related to oxidative stress (aldo-keto reductase, peroxiredoxin-1, NAD(+)-dependent isocitrate dehydrogenase, iron-responsive element-binding protein-1 and serum albumin), two participate in cytoskeleton organization (l-plastin and ezrin) and three are assigned to metabolic functions (creatine kinase, ornithine aminotransferase and fructose-1,6-bisphosphatase). CONCLUSION: The proteins related to IF/TA and involved in oxidative stress, cytoskeleton organization and metabolic functions may correspond with novel therapeutic targets.
Authors: Line Aas Mortensen; Anne Marie Svane; Mark Burton; Claus Bistrup; Helle Charlotte Thiesson; Niels Marcussen; Hans Christian Beck Journal: Int J Mol Sci Date: 2020-03-30 Impact factor: 5.923