Eplerenone Ameliorates Cell Pyroptosis in Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction.
Aldosterone
Contralateral kidney
Nod-like receptor pyrin-containing 3 inflammasomes
Pyroptosis
Unilateral ureteral obstruction
Journal
Nephron
ISSN: 2235-3186
Titre abrégé: Nephron
Pays: Switzerland
ID NLM: 0331777
Informations de publication
Date de publication:
2019
2019
Historique:
received:
30
09
2018
accepted:
01
02
2019
pubmed:
26
2
2019
medline:
1
7
2020
entrez:
26
2
2019
Statut:
ppublish
Résumé
The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inflammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats. Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies. We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL. Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.
Sections du résumé
BACKGROUND
The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inflammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats.
METHODS
Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies.
RESULTS
We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL.
CONCLUSION
Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.
Identifiants
pubmed: 30799394
pii: 000497489
doi: 10.1159/000497489
doi:
Substances chimiques
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, rat
0
Receptors, Mineralocorticoid
0
Eplerenone
6995V82D0B
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
233-242Informations de copyright
© 2019 S. Karger AG, Basel.