Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon’s effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstructi...

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Autores principales: Fei Chen, Yu Xie, Qin Lv, Wei Zou, Liyan Xiong
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Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/1865372fb72a4019b97e9b26dc69b358
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spelling oai:doaj.org-article:1865372fb72a4019b97e9b26dc69b3582021-11-11T14:23:40ZCurcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction0886-022X1525-604910.1080/0886022X.2021.1997764https://doaj.org/article/1865372fb72a4019b97e9b26dc69b3582021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/0886022X.2021.1997764https://doaj.org/toc/0886-022Xhttps://doaj.org/toc/1525-6049In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon’s effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.Fei ChenYu XieQin LvWei ZouLiyan XiongTaylor & Francis Grouparticlecurcumindragonrenal fibrosisunilateral ureteral obstructionrepulsive guidance molecule bDiseases of the genitourinary system. UrologyRC870-923ENRenal Failure, Vol 43, Iss 1, Pp 1496-1505 (2021)
institution DOAJ
collection DOAJ
language EN
topic curcumin
dragon
renal fibrosis
unilateral ureteral obstruction
repulsive guidance molecule b
Diseases of the genitourinary system. Urology
RC870-923
spellingShingle curcumin
dragon
renal fibrosis
unilateral ureteral obstruction
repulsive guidance molecule b
Diseases of the genitourinary system. Urology
RC870-923
Fei Chen
Yu Xie
Qin Lv
Wei Zou
Liyan Xiong
Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
description In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon’s effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.
format article
author Fei Chen
Yu Xie
Qin Lv
Wei Zou
Liyan Xiong
author_facet Fei Chen
Yu Xie
Qin Lv
Wei Zou
Liyan Xiong
author_sort Fei Chen
title Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
title_short Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
title_full Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
title_fullStr Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
title_full_unstemmed Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
title_sort curcumin mediates repulsive guidance molecule b (rgmb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/1865372fb72a4019b97e9b26dc69b358
work_keys_str_mv AT feichen curcuminmediatesrepulsiveguidancemoleculebrgmbinthetreatmentmechanismofrenalfibrosisinducedbyunilateralureteralobstruction
AT yuxie curcuminmediatesrepulsiveguidancemoleculebrgmbinthetreatmentmechanismofrenalfibrosisinducedbyunilateralureteralobstruction
AT qinlv curcuminmediatesrepulsiveguidancemoleculebrgmbinthetreatmentmechanismofrenalfibrosisinducedbyunilateralureteralobstruction
AT weizou curcuminmediatesrepulsiveguidancemoleculebrgmbinthetreatmentmechanismofrenalfibrosisinducedbyunilateralureteralobstruction
AT liyanxiong curcuminmediatesrepulsiveguidancemoleculebrgmbinthetreatmentmechanismofrenalfibrosisinducedbyunilateralureteralobstruction
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