HL156A, a novel pharmacological agent with potent adenosine-monophosphate-activated protein kinase (AMPK) activator activity ameliorates renal fibrosis in a rat unilateral ureteral obstruction model.
PLoS One
; 13(8): e0201692, 2018.
Article
en En
| MEDLINE
| ID: mdl-30161162
ABSTRACT
BACKGROUND:
Renal fibrosis is characterized by excessive production and deposition of extracellular matrix (ECM), which leads to progressive renal failure. Adenosine-monophosphate-activated protein kinase (AMPK) is a highly conserved kinase that plays a key role in Smad-3 signaling. Here, we examined the effect of a novel AMPK activator, HL156A, on the inhibition of renal fibrosis in in vivo and in vitro models.METHODS:
Unilateral ureteral obstruction (UUO) was induced in male Wistar rats. Rats with UUO were administered HL156A (20mg/kg/day), and then the kidneys were harvested 10 days after ligation for further analysis.RESULTS:
In the rat UUO model, HL156A attenuated ECM protein deposition. After HL156A treatment, expressions of TGF-ß1, p-Smad3, α-SMA, fibronectin, and type IV collagen were suppressed, and E-cadherin expression was up-regulated. In the in vitro experiment, NRK52E cells were treated with HL156A before TGF-ß1 stimulation. The inhibitory effects of HL156A upon the signaling pathways and markers of the epithelial-to-mesenchymal transition (EMT) were analyzed. In TGF-ß1-treated NRK-52E cells, HL156A co-treatment inhibited the TGF-ß1-induced Smad3 signaling pathway and EMT markers.CONCLUSION:
Taken together, the above findings suggest that HL156A, a novel AMPK activator, ameliorates renal fibrosis in vivo and in vitro.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirrolidinas
/
Obstrucción Ureteral
/
Proteínas Quinasas Activadas por AMP
/
Guanidinas
/
Riñón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2018
Tipo del documento:
Article