Abstract
BackgroundRenal 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.MethodsUnilateral 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.ResultsIn the rat UUO model, HL156A attenuated ECM protein deposition. After HL156A treatment, expressions of TGF-β1, 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-β1 stimulation. The inhibitory effects of HL156A upon the signaling pathways and markers of the epithelial-to-mesenchymal transition (EMT) were analyzed. In TGF-β1-treated NRK-52E cells, HL156A co-treatment inhibited the TGF-β1-induced Smad3 signaling pathway and EMT markers.ConclusionTaken together, the above findings suggest that HL156A, a novel AMPK activator, ameliorates renal fibrosis in vivo and in vitro.
Highlights
Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is the final common pathway of many kidney diseases[1]
The above findings suggest that HL156A, a novel Adenosine monophosphate protein kinase (AMPK) activator, ameliorates renal fibrosis in vivo and in vitro
We showed that HL156A had a protective effect against peritoneal fibrosis (PF)[22]
Summary
Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is the final common pathway of many kidney diseases[1]. Tubulointerstitial fibrosis is associated with epithelial-mesenchymal transition (EMT)[2], and synthesis of extracellular matrix (ECM). Transforming growth factor-β (TGF-β) signaling is one of the most important pathways associated with renal fibrosis by activating its downstream Smad signaling pathway[4], [5], [6]. UUO is a well-known model of renal fibrosis[8], [9]. UUO causes renal metabolic changes, leading to tubular injury and renal inflammation, characterized by macrophage infiltration[10]. Renal fibrosis is characterized by excessive production and deposition of extracellular matrix (ECM), which leads to progressive renal failure. We examined the effect of a novel AMPK activator, HL156A, on the inhibition of renal fibrosis in in vivo and in vitro models
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