Indoxyl Sulfate Aggravates Podocyte Damage through the TGF-ß1/Smad/ROS Signalling Pathway.
Kidney Blood Press Res
; 49(1): 385-396, 2024.
Article
en En
| MEDLINE
| ID: mdl-38735279
ABSTRACT
INTRODUCTION:
Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor ß1 (TGF-ß1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulphate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress, and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-ß1 signalling pathway is still unclear.METHODS:
In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, and α-SMA by quantitative real-time PCR (qRT-PCR) and Western blotting after siRNA-mediated TGF-ß1 silencing, TGF-ß1 overexpression, and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, small mother against decapentaplegic (Smad)2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions.RESULTS:
The results indicated that nephrin, synaptopodin, CD2AP, and SRGAP2a expressions were significantly upregulated, and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-ß1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP, and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-ß1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP, and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7, and NOX4; and increased ROS production in podocytes.CONCLUSION:
This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP, and SRGAP2a by regulating the ROS and TGF-ß1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Especies Reactivas de Oxígeno
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Nefropatías Diabéticas
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Podocitos
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Factor de Crecimiento Transformador beta1
/
Indicán
Límite:
Animals
Idioma:
En
Revista:
Kidney Blood Press Res
Asunto de la revista:
NEFROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China