Genetic and pharmacological inhibition of fatty acid-binding protein 4 alleviated inflammation and early fibrosis after toxin induced kidney injury.
Int Immunopharmacol
; 96: 107760, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33991998
ABSTRACT
Considerable data have suggested that acute kidney injury (AKI) is often incompletely repaired and could lead to chronic kidney disease (CKD). As we known, toxin-induced nephropathy triggers the rapid production of proinflammatory mediators and the prolonged inflammation allows the injured kidneys to develop interstitial fibrosis. In our previous study, fatty acid-binding protein 4 (Fabp4) has been reported to be involved in the process of AKI. However, whether Fabp4 plays crucial roles in toxin-induced kidney injury remained unclear. To explore the effect and mechanism of Fabp4 on toxin induced kidney injury, folic acid (FA) and aristolochic acid (AA) animal models were used. Both FA and AA injected mice developed severe renal dysfunction and dramatically inflammatory response (IL-6, MCP1 and TNF-a), which further lead to early fibrosis confirmed by the accumulation of extracellular matrix proteins (α-Sma, Fn, Col1 and Col4). Importantly, we found that FA and AA induced-kidney injury triggered the high expression of Fabp4 mRNA/protein in tubular epithelial cells. Furthermore, pharmacological and genetic inhibition of Fabp4 significantly attenuated FA and AA induced renal dysfunction, pathological damage, and early fibrosis via the regulation of inflammation, which is mediated by suppressing p-p65/p-stat3 expression via enhancing Pparγ activity. In summary, Fabp4 in tubular epithelial cells exerted the deleterious effects during the recovery of FA and AA induced kidney injury and the inhibition of Fabp4 might be an effective therapeutic strategy against the progressive AKI.
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MEDLINE
Assunto principal:
Pirazóis
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Compostos de Bifenilo
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Fibrose
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Proteínas de Ligação a Ácido Graxo
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Injúria Renal Aguda
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Inflamação
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article