Deletion of Alox15 improves kidney dysfunction and inhibits fibrosis by increased PGD2 in the kidney.
Clin Exp Nephrol
; 25(5): 445-455, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33595729
ABSTRACT
BACKGROUND:
Lipid-metabolizing enzymes and their metabolites affect inflammation and fibrosis, but their roles in chronic kidney disease (CKD) have not been completely understood.METHODS:
To clarify their role in CKD, we measured the mRNA levels of major lipid-metabolizing enzymes in 5/6 nephrectomized (Nx) kidneys of C57BL/6 J mice. Mediator lipidomics was performed to reveal lipid profiles of CKD kidneys.RESULTS:
In 5/6 Nx kidneys, both mRNA and protein levels of Alox15 were higher when compared with those in sham kidneys. With respect to in situ hybridization, the mRNA level of Alox15 was higher in renal tubules of 5/6 Nx kidneys. To examine the role of Alox15 in CKD pathogenesis, we performed 5/6 Nx on Alox15-/- mice. Alox15-/- CKD mice exhibited better renal functions than wild-type mice. Interstitial fibrosis was also inhibited in Alox15-/- CKD mice. Mediator lipidomics revealed that Alox15-/- CKD mouse kidneys had significantly higher levels of PGD2 than the control. To investigate the effects of PGD2 on renal fibrosis, we administered PGD2 to TGF-ß1-stimulated NRK-52E cells and HK-2 cells, which lead to a dose-dependent suppression of type I collagen and αSMA in both cell lines.CONCLUSION:
Increased PGD2 in Alox15-/- CKD mouse kidneys could inhibit fibrosis, thereby resulting in CKD improvement. Thus, Alox15 inhibition and PGD2 administration may be novel therapeutic targets for CKD.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 12-Lipoxigenase
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Araquidonato 15-Lipoxigenase
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Prostaglandina D2
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Insuficiência Renal Crônica
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Metabolismo dos Lipídeos
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Rim
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Clin Exp Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão