Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury.
EBioMedicine
; 19: 73-83, 2017 May.
Article
en En
| MEDLINE
| ID: mdl-28434946
ABSTRACT
Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R) are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40ml/min/1.73sq.m.), and increased interstitial fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells cultured under high glucose conditions. In mice, P2X7R-deficiency prevented glomerular macrophage attraction and collagen IV deposition; however, the more severe interstitial inflammation and fibrosis often seen in human diabetic kidney diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor (AZ11657312) can reduce renal macrophage accrual following the establishment of hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest that P2X7R activation may contribute to the high prevalence of kidney disease found in diabetics.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 1
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Nefropatías Diabéticas
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Receptores Purinérgicos P2X7
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Hiperglucemia
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Riñón
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
EBioMedicine
Año:
2017
Tipo del documento:
Article