Activation of liver X receptor suppresses osteopontin expression and ameliorates nephrolithiasis.
J Cell Physiol
; 234(8): 14109-14122, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-30623435
ABSTRACT
Nephrolithiasis is a common disease of the urinary system, of which idiopathic calcium oxalate (CaOx) kidney stones, in particular, are one of the special types. In the initial stages of CaOx kidney stone formation, Randall's plaques (RPs) develop. Liver X receptors (LXRs) inhibit oxidative stress and inï¬ammatory in other diseases; nevertheless, the role of LXRs in nephrolithiasis has yet to be elucidated. In this study, the role of LXRs in the progression of RP formation was investigated. Microarray analysis revealed that LXR/RXR levels were significantly greater in low-plaque tissues (<5%) than in high-plaque tissues (>5%), confirming the link between LXR activation and RP formation. Correspondingly, expression levels of two LXR target genes, LXRα and LXRß, were lower in high-plaque tissues than in low-plaque tissues. In vitro, LXR agonist alleviated calcium oxalate monohydrate-induced cellular calcium deposits and apoptosis. LXR activation decreased reactive oxygen species production and gene expression of inflammatory mediators, including osteopontin that has recently been demonstrated to correlate with the development of RPs. Moreover, p38 MAPK and JNK signaling may mediate LXR-regulated expression in HK-2 cells. In an animal model, the deposition was reduced by activating LXR, and osteopontin expression was also inhibited. Our findings suggest a role for LXRs in the progression of idiopathic CaOx kidney stones; LXR agonists may have therapeutic potential for the treatment of nephrolithiasis.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cálculos Renales
/
Nefrolitiasis
/
Osteopontina
/
Receptores X del Hígado
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Riñón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Cell Physiol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China