PURPOSE: Our aim was to investigate the role of tranilast in transforming growth factor (TGF) β/Smad pathways using a rat model of chronic cyclosporine (CsA) nephrotoxicity. METHODS: Thirty Sprague-Dawley (SD) rats were equally randomized in to 5 groups for gavage treatments daily for 4 weeks: normal control (N), olive oil; CsA (25 mg/kg), (M) CsA plus low-dose tranilast group (T1; CsA 25 mg/kg and tranilast 100 mg/kg); CsA plus medium-dose tranilast group (T2; CsA 25 mg/kg and tranilast 200 mg/kg); and CsA plus high-dose tranilast group (T4; CsA 25 mg/kg and tranilast 400 mg/kg). Kidneys were harvested at the end of the fourth week. TGF-β1 as well as Smad3 and Smad7 were detected by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: The administration of tranilast decreased the expression of TGF-β1 and Smad3 by CsA-treated rats, whereas it increased both mRNA and protein levels of Smad7. Semiquantitative analysis of mRNA production revealed these treatments to markedly reduce the amount of TGF-β1: T1: 0.8452 ± 0.0825 vs 0.8529 ± 0.0606 (P < .05); T2: 0.8414 ± 0.0696 vs 0.8529 ± 0.0606 (P < .05); T4: 0.8336 ± 0.0592 vs 0.8529 ± 0.0606 (P < .05). For Smad3: T1: 0.8581 ± 0.0328 vs 0.8613 ± 0.0542 (P < .05); T2: 0.8528 ± 0.0599 vs 0.8613 ± 0.0542 (P < .05); T4: 0.8436 ± 0.0185 vs 0.8613 ± 0.0542 (P < .05). The significantly elevated dose-dependent amounts of Smad7 were: T1: 0.9026 ± 0.0522 vs 0.8678 ± 0.0246, (P < .05); T2: 0.9087 ± 0.0506 vs 0.8678 ± 0.0246 (P < .05); T4: 0.9151 ± 0.0793 vs 0.8678 ± 0.0246 (P < .05). CONCLUSION: Regulation of TGF-β/Smad pathways is one of the mechanisims by which tranilast mitigates the progression of chronic CsA nephrotoxicity in rats.
PURPOSE: Our aim was to investigate the role of tranilast in transforming growth factor (TGF) β/Smad pathways using a rat model of chronic cyclosporine (CsA) nephrotoxicity. METHODS: Thirty Sprague-Dawley (SD) rats were equally randomized in to 5 groups for gavage treatments daily for 4 weeks: normal control (N), olive oil; CsA (25 mg/kg), (M) CsA plus low-dose tranilast group (T1; CsA 25 mg/kg and tranilast 100 mg/kg); CsA plus medium-dose tranilast group (T2; CsA 25 mg/kg and tranilast 200 mg/kg); and CsA plus high-dose tranilast group (T4; CsA 25 mg/kg and tranilast 400 mg/kg). Kidneys were harvested at the end of the fourth week. TGF-β1 as well as Smad3 and Smad7 were detected by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: The administration of tranilast decreased the expression of TGF-β1 and Smad3 by CsA-treated rats, whereas it increased both mRNA and protein levels of Smad7. Semiquantitative analysis of mRNA production revealed these treatments to markedly reduce the amount of TGF-β1: T1: 0.8452 ± 0.0825 vs 0.8529 ± 0.0606 (P < .05); T2: 0.8414 ± 0.0696 vs 0.8529 ± 0.0606 (P < .05); T4: 0.8336 ± 0.0592 vs 0.8529 ± 0.0606 (P < .05). For Smad3: T1: 0.8581 ± 0.0328 vs 0.8613 ± 0.0542 (P < .05); T2: 0.8528 ± 0.0599 vs 0.8613 ± 0.0542 (P < .05); T4: 0.8436 ± 0.0185 vs 0.8613 ± 0.0542 (P < .05). The significantly elevated dose-dependent amounts of Smad7 were: T1: 0.9026 ± 0.0522 vs 0.8678 ± 0.0246, (P < .05); T2: 0.9087 ± 0.0506 vs 0.8678 ± 0.0246 (P < .05); T4: 0.9151 ± 0.0793 vs 0.8678 ± 0.0246 (P < .05). CONCLUSION: Regulation of TGF-β/Smad pathways is one of the mechanisims by which tranilast mitigates the progression of chronic CsAnephrotoxicity in rats.
Authors: Oliver Beetz; Joline Kolb; Benjamin Buck; Britta Trautewig; Kai Timrott; Florian W R Vondran; Ingrid Meder; Corinna Löbbert; Joachim Hundrieser; Jürgen Klempnauer; Hüseyin Bektaş; Thorsten Lieke Journal: PLoS One Date: 2019-08-22 Impact factor: 3.240