The IL-8-CXCR1/2 axis contributes to diabetic kidney disease.
Adult
Animals
Case-Control Studies
Cells, Cultured
Cohort Studies
Diabetes Mellitus, Experimental
/ genetics
Diabetes Mellitus, Type 2
/ complications
Diabetic Nephropathies
/ genetics
Humans
Interleukin-8
/ genetics
Italy
Kidney
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Podocytes
/ metabolism
Receptors, CXCR
/ physiology
Receptors, Interleukin-8A
/ genetics
Receptors, Interleukin-8B
/ genetics
Signal Transduction
/ physiology
CXCR1
CXCR1/2 blockade
CXCR2
Diabetic kidney disease
IL-8
Podocyte
Type 2 diabetes
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
15
02
2021
revised:
29
04
2021
accepted:
01
06
2021
pubmed:
8
6
2021
medline:
6
10
2021
entrez:
7
6
2021
Statut:
ppublish
Résumé
Inflammation has a major role in diabetic kidney disease. We thus investigated the role of the IL-8-CXCR1/2 axis in favoring kidney damage in diabetes. Urinary IL-8 levels were measured in 1247 patients of the Joslin Kidney Study in type 2 diabetes (T2D). The expression of IL-8 and of its membrane receptors CXCR1/CXCR2 was quantified in kidney tissues in patients with T2D and in controls. The effect of CXCR1/2 blockade on diabetic kidney disease was evaluated in db/db mice. IL-8 urinary levels were increased in patients with T2D and diabetic kidney disease, with the highest urinary IL-8 levels found in the patients with the largest decline in glomerular filtration rate, with an increased albumin/creatine ratio and the worst renal outcome. Moreover, glomerular IL-8 renal expression was increased in patients with T2D, as compared to controls. High glucose elicits abundant IL-8 secretion in cultured human immortalized podocytes in vitro. Finally, in diabetic db/db mice and in podocytes in vitro, CXCR1/2 blockade mitigated albuminuria, reduced mesangial expansion, decreased podocyte apoptosis and reduced DNA damage. The IL-8- CXCR1/2 axis may have a role in diabetic kidney disease by inducing podocyte damage. Indeed, targeting the IL-8-CXCR1/2 axis may reduce the burden of diabetic kidney disease.
Identifiants
pubmed: 34097917
pii: S0026-0495(21)00104-9
doi: 10.1016/j.metabol.2021.154804
pii:
doi:
Substances chimiques
Interleukin-8
0
Receptors, CXCR
0
Receptors, Interleukin-8A
0
Receptors, Interleukin-8B
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154804Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.