DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway.
J Endocrinol Invest
; 47(6): 1531-1544, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38147289
ABSTRACT
BACKGROUND:
Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury.METHODS:
Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed.RESULTS:
Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2).CONCLUSIONS:
This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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FN-kappa B
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Factor de Crecimiento Transformador beta
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Ácido Palmítico
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Receptor Toll-Like 4
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Factor 88 de Diferenciación Mieloide
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Túbulos Renales
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Endocrinol Invest
Año:
2024
Tipo del documento:
Article
País de afiliación:
China