Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells

Gaedeke, Jens; Noble, Nancy A.; Border, Wayne A.

doi:10.1111/j.1523-1755.2004.00713.x

Cited by 138 publications

(116 citation statements)

References 28 publications

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“…PAI-1 can be induced by TGF-␤1 in rodent kidneys and in cultured mesangial cells. 22,23 TGF-␤1 transgenic mice developed expanded ECM, which was accompanied by increased levels of PAI-1 in vivo. 22 We previously reported upregulation of TGF-␤1 mRNA in glomeruli by ISH that parallels the accumulation of ECM proteins in TSLP mice 24 and now show that this correlates with upregulated PAI-1 expression.…”

Section: Discussionmentioning

confidence: 99%

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Taneda¹,

Hudkins²,

Mühlfeld³

et al. 2008

Journal of the American Society of Nephrology

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Thymic stromal lymphopoietin (TSLP) transgenic mice develop cryoglobulin-associated membranoproliferative glomerulonephritis, characterized by renal monocyte/macrophage infiltration, marked expansion of extracellular matrix, and variable intraluminal and mesangial deposits of cryoglobulins. A microarray approach was used to study global gene expression in glomerular RNA obtained from these mice, as well as from combined TSLP transgenic and

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Section: Discussionmentioning

confidence: 99%

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Taneda¹,

Hudkins²,

Mühlfeld³

et al. 2008

Journal of the American Society of Nephrology

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“…14,18,20) Likewise, rapamycin reduced fibrosis and attenuated disease progression in rat models of liver cirrhosis and pulmonary fibrosis. 21,22) Therefore, these data suggest that TGF-β1 contributes to EMT by activating the Akt/mTOR pathway, and the inhibition of this pathway can restrain organ fibrosis.…”

Section: Curcumin Suppresses Epithelial-mesenchymal Transition Of Renmentioning

confidence: 99%

“…Although it is reported that curcumin can block the TGF-β signaling cascade at multiple sites in renal cells, 22) it is still largely unknown whether the Akt/mTOR signaling pathway is involved in the curcumin-induced anti-fibrotic effect. Therefore, we presume that curcumin prevents TGF-β1-induced EMT through the inhibition of the AKt/mTOR signaling pathway.…”

Section: Curcumin Suppresses Epithelial-mesenchymal Transition Of Renmentioning

confidence: 99%

“…Curcumin is shown to have an antifibrogenic effect, and can prevent fibrosis in the liver and lung, 6,[8][9][10]22) but the underlying mechanisms by which it works remain to be elucidated. Although it is reported that curcumin can block the TGF-β signaling cascade at multiple sites in renal cells, 22) it is still largely unknown whether the Akt/mTOR signaling pathway is involved in the curcumin-induced anti-fibrotic effect.…”

Section: Curcumin Suppresses Epithelial-mesenchymal Transition Of Renmentioning

confidence: 99%

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Curcumin Suppresses Epithelial–Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway

Zhu

Chen

Zhu

et al. 2017

Biological & Pharmaceutical Bulletin

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Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of E-cadherin, cytokeratin, vimentin, alpha smooth muscle actin (α-SMA), fibroblast-specific protein 1 (FSP1) and key proteins of Akt/ mammalian target of rapamycin (mTOR) pathway were analyzed by immunocytochemistry, real-time PCR and Western blot. Low dose curcumin (3.125 and 25 µmol/L) effectively promoted HKC proliferation. When HKCs were co-incubated with TGF-β1 and curcumin for 72 h, curcumin maintained the epithelial morphology in a dose-dependent manner, decreased expression of vimentin, α-SMA and FSP1 normally induced by TGF-β1, and increased expression of E-cadherin, cytokeratin. Importantly, we found that curcumin reduced Akt, mTOR and P70S6K phosphorylation, effectively suppressing the activity of the Akt/mTOR pathway in HKCs. Curcumin also promoted HKC proliferation, and antagonized TGF-β1-driven EMT through the inhibition of Akt/mTOR pathway activity, which may suggest an alternative therapy for renal fibrosis.

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“…Este efecto es producido por el metabolismo del CCl 4 que causa la peroxidación lipídica y la producción de los radicales libres (33) , conduciendo a la disfunción de los mismos, la liberación de ROS, y mediadores fibrogénicos e inflamatorios. Tras la lesión en el hígado, las células hepáticas producen colágeno fibrilar dentro del tejido dañado (34) , induciendo la inflamación, promoviendo la progresión de la fibrogénesis hepática y causando la necrosis de los hepatocitos (35) . El extracto acuoso liofilizado de C. longa 200 mg, mejoró los cambios patológicos producidos por CCl 4 , mostrando un parénquima hepático normal hacia la normalización de las funciones celulares y restauración de los niveles séricos de AST, ALT y ALP.…”

Section: Discussionunclassified

Análisis fitoquímico, actividad antioxidante y hepatoprotectora del extracto acuoso liofilizado de Curcuma longa en lesiones hepáticas inducidas con tetraclorometano en ratas albinas

Canelo-Saldaña

Mendoza-Gardini

Villacrés-Vallejo

et al. 2017

Rev. per. med. integr.

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765REV PERU MED INTEGRATIVA.2017;2(3):765-72. Citar comoCanelo-Saldaña P, Mendoza-Gardini Y, Villacrés Vallejo J, Aranda-Ventura J, González-Aspajo G. Análisis fitoquímico, actividad antioxidante y hepatoprotector del extracto acuoso liofilizado de Curcuma longa en lesiones hepáticas inducidas con tetraclorometano, en ratas albinas Rev Peru Med Integrativa.2017;2(3):765-72. Historia del artículo Información del artículo ResumenObjetivos. Realizar un análisis fitoquímico y describir la actividad hepatoprotectora y antioxidante del extracto de rizomas de Curcuma longa L. (C. longa) en un modelo murino. Materiales y métodos. La actividad antioxidante in vitro del extracto acuoso liofilizado de rizoma de C. longa L. (Fam: Zingiberaceae) se evaluó con el método de DPPH, además, también se realizó el análisis fitoquímico de tres solventes de extracción (ExEt, ExDCM y ExH 2 O). El ensayo in vivo se realizó en ratas albinas cepa Holtzman. Se formaron cinco grupos de tratamiento: (control normal); (control-CCl 4 ); (Control positivo); (C. longa 100 mg/kg) y (C. longa 200 mg/kg), que fueron inducidos con CCl 4 para desarrollar daño hepático. Este modelo permitió medir el efecto protector de los extractos sobre los marcadores bioquímicos (AST, ALT y ALP) en sangre. Posteriormente, se realizó un examen histopatológico de las secciones hepáticas para apoyar la inducción de la hepatoxicidad y la eficacia hepatoprotectora. Resultados.El extracto mostró un poder reductor mucho menor que el ácido ascórbico, en el tamizaje fitoquímico se encontraron compuestos fenólicos, triterpenos, quinonas, cumarinas y flavonoides, además la cantidad de curcumina encontrada fue de 0,4%-0,6%. El extracto liofilizado de C.longa mostró un efecto protector significativo (P<0,05), disminuyendo la actividad enzimática de los marcadores hepatoespecíficos. Los niveles elevados de enzimas séricas AST, ALT y ALP, se hallaron restablecidas hacia la normalización, de manera dosis dependiente, con el máximo efecto protector a dosis de 200 mg/kg. Las observaciones histopatológicas soportan las evidencias bioquímicas de hepatoprotección. Estos efectos fueron comparables a la droga estándar, silimarina. Conclusiones. Los resultados presentados en este estudio revelan fuertemente el efecto protector del extracto liofilizado de C. longa, cultivada en la región Loreto, frente a daño hepático inducido por CCl 4 en experimentación animal. Palabras clave: Curcuma, Antioxidantes, Curcumina, Tetracloruro de Carbono, Hepatoprotector (Fuente: DeCS).Phytochemical analysis, antioxidant and hepatoprotective activity of liofilizated aqueous extract of Curcuma longa on albino rats liver injury induced by tetrachloromethane AbstractObjectives. To develop a phytochemical analysis and describe the hepatoprotective and antioxidant activities of Curcuma longa (C. longa) rhizomes extract in a murine model. Materials and methods. In vitro antioxidant activity of aqueous liofilizated extract of rhizome of C. longa L. (Fam: Zingiberaceae) was evaluated by DPPH assays, and the phyto...

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Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells

Abstract: Curcumin blocks TGF-beta's profibrotic actions on renal fibroblasts through down-regulation of TbetaRII, and through partial inhibition of c-jun activity. These in vitro data suggest that curcumin might be an effective antifibrotic drug in the treatment of chronic kidney disease.

Cited by 138 publications

References 28 publications

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Curcumin Suppresses Epithelial–Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway

Análisis fitoquímico, actividad antioxidante y hepatoprotectora del extracto acuoso liofilizado de Curcuma longa en lesiones hepáticas inducidas con tetraclorometano en ratas albinas

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Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells

Abstract: Curcumin blocks TGF-beta's profibrotic actions on renal fibroblasts through down-regulation of TbetaRII, and through partial inhibition of c-jun activity. These in vitro data suggest that curcumin might be an effective antifibrotic drug in the treatment of chronic kidney disease.

Cited by 138 publications

References 28 publications

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis

Curcumin Suppresses Epithelial–Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway

Análisis fitoquí­mico, actividad antioxidante y hepatoprotectora del extracto acuoso liofilizado de Curcuma longa en lesiones hepáticas inducidas con tetraclorometano en ratas albinas

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Análisis fitoquímico, actividad antioxidante y hepatoprotectora del extracto acuoso liofilizado de Curcuma longa en lesiones hepáticas inducidas con tetraclorometano en ratas albinas