CPT1a downregulation protects against cholesterol-induced fibrosis in tubular epithelial cells by downregulating TGFß-1 and inflammasome.
Biochem Biophys Res Commun
; 517(4): 715-721, 2019 10 01.
Article
en En
| MEDLINE
| ID: mdl-31405564
BACKGROUND: Dyslipidemia causes renal damage; however, the detailed molecular mechanism has not been clarified. It is known that carnitine palmitoyl transferase 1-a (CPT1a) gene encodes an enzyme involved in fatty acid oxidation and, therefore, lipid content. In the present study, we investigated whether the accumulation of lipids induced by 7-ketocholesterol (7-KC) in tubular epithelial cells produce a fibrotic and inflammatory response through CPT1a. METHODS: Using an epithelial cell line, NRK-52E, we determine if intracellular accumulation of 7-KC modulates profibrotic and inflammatory events through CPT1a gene expression. In addition, the direct effects of CPT1a genetic modification has been studied. RESULTS: Our results revealed that high levels of 7-KC induce increased expression of CPT1a, TGF-ß1, α- SMA and NLRP3 that was correlated with lipid content. GW3965 treatment, which have shown to facilitate the efflux of cholesterol, eliminated the intracellular lipid droplets of 7-KC laden cells and decreased the expression of CPT1a, TGF-ß1, α- SMA and NLRP3. Furthermore, CPT1a Knockdown and C75 pre-treatment increased lipid content but decreased TGF-ß1, α- SMA and NLRP3. CONCLUSIONS: Our findings reveal that the profibrotic effect of 7-KC on renal epithelial cells are mediated by CPT1a overexpression, which acts on TGF-ß1, α-SMA and NLRP3. Thus, CPT1a downregulation protects against 7-KC-induced fibrosis in tubular epithelial cells by downregulating TGF-ß1, α- SMA and NLRP3.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carnitina O-Palmitoiltransferasa
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Regulación hacia Abajo
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Células Epiteliales
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Factor de Crecimiento Transformador beta1
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Inflamasomas
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Túbulos Renales Proximales
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Estados Unidos