Transforming growth factor-beta1, vascular endothelial growth factor, and bone morphogenic protein-7 expression in tacrolimus-induced nephrotoxicity in rats.
The aim of our study was to investigate transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), and bone morphogenic protein-7 (BMP-7) expression in the rat model of chronic tacrolimus (TAC) toxicity compared to healthy controls. Seventeen male Wistar rats were divided into two groups: group 1 animals were healthy controls and Group 2 animals were treated with TAC (1 mg/kg per day intraperitoneally for 8 weeks). At the end of the study period the animals were sacrificed following renal function studies including blood urea nitrogen (BUN), serum creatinine, and creatinine clearance, and renal tissues were examined by light microscopy for the findings of tacrolimus toxicity, specifically for afferent arteriolopathy and interstitial fibrosis. TGF-beta1, VEGF, and BMP-7 expression were assessed by semiquantitative scoring of the immunohistochemically stained specimens. Mean TAC levels were 5.53 +/- 2.38 ng/mL in group 2. BUN, creatinine levels, and creatinine clearance were 57.99 +/- 11.13 vs 39.49 +/- 5.64 mg/dL; 0.60 +/- 0.16 vs 0.65 +/- 0.09 mg/dL; 0.97 +/- 0.39 vs 1.17 +/- 0.32 mL/min in group 2 versus group 1. Only the BUN level was significantly higher in group 2 compared to group 1. Afferent arteriolopathy and interstitial fibrosis were significantly increased in group 2 compared to group 1. TGF-beta1 and VEGF expression was significantly increased while BMP-7 expression was significantly decreased in group 2 versus group 1. In conclusion, our findings suggest that TAC-induced nephrotoxicity is associated with increased TGF-beta1 and VEGF and decreased BMP-7 expression.
Department of Pathology, Division of Nephrology, Marmara University Medical School, Istanbul, Turkey. betulogutmen@yahoo.com
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Tuğlular
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Cakalağaoğlu
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Ozener
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Akoğlu
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001806:Blood Urea Nitrogen; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D007166:Immunosuppressive Agents; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D003404:Creatinine; D016559:Tacrolimus