Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases.
BMC Nephrol
; 21(1): 402, 2020 09 18.
Article
en En
| MEDLINE
| ID: mdl-32948146
ABSTRACT
BACKGROUND:
Dipeptidyl peptidase-4 (DPP-4) is a serine protease that inhibits the degradation of glucagon-like peptide 1. DPP-4 inhibitors are used worldwide to treat type 2 diabetes mellitus and were recently shown to have pleiotropic effects such as anti-oxidant, anti-inflammatory, and anti-fibrotic actions. DPP-4 inhibitors improve albuminuria and renal injury including glomerular damage independent of its hypoglycemic effect. Although DPP-4 is mainly expressed in the kidney, the physiological function of DPP-4 remains unclear.METHODS:
The localization of renal DPP-4 activity was determined in human renal biopsy specimens with glycyl-1-prolyl-4-methoxy-2-naphthylamide and the effects of a DPP-4 inhibitor were examined in human cultured podocyte.RESULTS:
DPP-4 activity under normal conditions was observed in some Bowman's capsular epithelial cells and proximal tubules, but not in the glomerulus. DPP-4 activity was observed in crescent formation in anti-neutrophil myeloperoxidase cytoplasmic antigen antibody nephritis, nodular lesions in diabetic nephropathy, and some podocytes in focal segmental glomerulosclerosis. Notably, the DPP-4 inhibitor saxagliptin suppressed DPP-4 activity in podocytes and the proximal tubules. To assess the effect of DPP-4 inhibitor on podocytes, human cultured podocytes were injured by Adriamycin, which increased DPP-4 activity; this activity was dose-dependently suppressed by saxagliptin. Treatment with saxagliptin maintained the structure of synaptopodin and RhoA. Saxagliptin also improved the detachment of podocytes.CONCLUSIONS:
DPP-4 activity induces degradation of synaptopodin and reduction of RhoA, resulting in destruction of the podocyte cytoskeleton. Saxagliptin may have pleiotropic effects to prevent podocyte injury.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adamantano
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Glomeruloesclerosis Focal y Segmentaria
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Dipeptidil Peptidasa 4
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Nefropatías Diabéticas
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Dipéptidos
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Podocitos
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Inhibidores de la Dipeptidil-Peptidasa IV
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Riñón
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Nefritis
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
BMC Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón