Ulinastatin inhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor β (TGF-β)/Smad signalling pathways

2013 ◽  
Vol 15 (2) ◽  
pp. 406-413 ◽  
Author(s):  
Xiao-hua Ning ◽  
Xiao-feng Ge ◽  
Yan Cui ◽  
Hui-xia An
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction ◽  
Signalling Pathways ◽  
Renal Interstitial Fibrosis

scholarly journals Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects on fibroblasts and tubular cells

2019 ◽  
Vol 316 (6) ◽  
pp. F1162-F1172 ◽  
Author(s):  
Qingqing Wei ◽  
Jennifer Su ◽  
Guie Dong ◽  
Ming Zhang ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Pathological Feature ◽  
Renal Interstitial Fibrosis ◽  
Tubular Cells ◽  
Glycolysis Inhibitors

Renal interstitial fibrosis is a common pathological feature of chronic kidney disease that may involve changes of metabolism in kidney cells. In the present study, we first showed that blockade of glycolysis with either dichloroacetate (DCA) or shikonin to target different glycolytic enzymes reduced renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Both inhibitors evidently suppressed the induction of fibronectin and collagen type I in obstructed kidneys, with DCA also showing inhibitory effects on collagen type IV and α-smooth muscle actin (α-SMA). Histological examination also confirmed less collagen deposition in DCA-treated kidneys. Both DCA and shikonin significantly inhibited renal tubular apoptosis but not interstitial apoptosis in UUO. Macrophage infiltration after UUO injury was also suppressed. Shikonin, but not DCA, caused obvious animal weight loss during UUO. To determine whether shikonin and DCA worked on tubular cells and/or fibroblasts, we tested their effects on cultured renal proximal tubular BUMPT cells and renal NRK-49F fibroblasts during hypoxia or transforming growth factor-β1 treatment. Although both inhibitors reduced fibronectin and α-SMA production in NRK-49F cells during hypoxia or transforming growth factor-β1 treatment, they did not suppress fibronectin and α-SMA expression in BUMPT cells. Altogether, these results demonstrate the inhibitory effect of glycolysis inhibitors on renal interstitial fibrosis. In this regard, DCA is more potent for fibrosis inhibition and less toxic to animals than shikonin.

scholarly journals Renoprotective Effects of Maslinic Acid on Experimental Renal Fibrosis in Unilateral Ureteral Obstruction Model via Targeting MyD88

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjuan Sun ◽  
Chang Hyun Byon ◽  
Dong Hyun Kim ◽  
Hoon In Choi ◽  
Jung Sun Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Adaptor Protein ◽  
Tissue Growth ◽  
Unilateral Ureteral Obstruction ◽  
Maslinic Acid

Maslinic acid (MA), also named crategolic acid, is a pentacyclic triterpene extracted from fruits and vegetables. Although various beneficial pharmacological effects of MA have been revealed, its effect on renal fibrosis remains unclear. This study was designed to clarify whether MA could attenuate renal fibrosis and determine the putative underlying molecular mechanisms. We demonstrated that MA-treated mice with unilateral ureteral obstruction (UUO) developed a histological injury of low severity and exhibited downregulated expression of fibrotic markers, including α-smooth muscle actin (α-SMA), vimentin, and fibronectin by 38, 44 and 40%, and upregulated expression of E-cadherin by 70% as compared with untreated UUO mice. Moreover, MA treatment restored the expression levels of α-SMA, connective tissue growth factor, and vimentin to 10, 7.8 and 38% of those induced by transforming growth factor (TGF)-β in NRK49F cells. MA decreased expression of Smad2/3 phosphorylation and Smad4 in UUO kidneys and TGF-β treated NRK49F cells (p < 0.05, respectively). Notably, MA specifically interferes with MyD88, an adaptor protein, thereby mitigating Smad4 nuclear expression (p < 0.01 compared to TGF-β treated group) and ameliorating renal fibrotic changes (p < 0.01 for each fibrotic markers compared to TGF-β induced cells). In addition, in the UUO model and lipopolysaccharide-induced NRK49F cells, MA treatment decreased the expression of IL-1β, TGF-α and MCP-1, ICAM-1, associated with the suppression of NF-κB signaling. These findings suggest that MA is a potential agent that can reduce renal interstitial fibrosis, to some extent, via targeting TGF-β/Smad and MyD88 signaling.

scholarly journals Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction

2000 ◽  
Vol 58 (6) ◽  
pp. 2301-2313 ◽  
Author(s):  
Akira Miyajima ◽  
Jie Chen ◽  
Cathy Lawrence ◽  
Steve Ledbetter ◽  
Robert A. Soslow ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction
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