scholarly journals Protective effects of SKLB023 on a mouse model of unilateral ureteral obstruction by the modulation of gut microbiota

RSC Advances ◽  
2018 ◽  
Vol 8 (70) ◽  
pp. 40232-40242
Author(s):  
Yanhuan Feng ◽  
Lingzhi Li ◽  
Fan Guo ◽  
Yanping Li ◽  
Yan Liang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Protective Effects ◽  
Common Pathway ◽  
The Common

Renal fibrosis is the common pathway underlying the progression of CKD to ESRD and quantitative and qualitative alterations in gut microbiota are noted in patients with CKD. Our results indicated SKLB023 drives the alteration of gut microbiota to attenuate renal fibrosis.

scholarly journals Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 141 ◽  
Author(s):  
Elena Martínez-Klimova ◽  
Omar Emiliano Aparicio-Trejo ◽  
Edilia Tapia ◽  
José Pedraza-Chaverri
Keyword(s):  
Renal Disease ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Unilateral Ureteral Obstruction ◽  
Chronic Obstructive ◽  
Common Pathway ◽  
Mesenchymal Transition ◽  
The Common ◽  
Progressive Renal Disease

Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β1), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included.

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

2008 ◽  
Vol 294 (3) ◽  
pp. F508-F517 ◽  
Author(s):  
Lin Wang ◽  
Ji-Yang Sophie Lee ◽  
Joon Hyeok Kwak ◽  
Yanjuan He ◽  
Sung Il Kim ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Low Dose ◽  
Tissue Injury ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
In Vivo Model ◽  
Obstructive Nephropathy ◽  
Protective Effects

Tubulointerstitial fibrosis is a hallmark of chronic progressive kidney disease leading to end-stage renal failure. An endogenous product of heme oxygenase activity, carbon monoxide (CO), has been shown to exert cytoprotection against tissue injury. Here, we explored the effects of exogenous administration of low-dose CO in an in vivo model of renal fibrosis induced by unilateral ureteral obstruction (UUO) and examined whether CO can protect against kidney injury. UUO in mice leads to increased extracellular matrix (ECM) deposition and tubulointerstitial fibrosis within 4 to 7 days. Kidneys of mice exposed to low-dose CO, however, had markedly reduced ECM deposition after UUO. Moreover, low-dose CO treatment inhibited the induction of α-smooth muscle actin (α-SMA) and major ECM proteins, type 1 collagen and fibronectin, in kidneys after UUO. In contrast, these anti-fibrotic effects of CO treatment were abrogated in mice carrying null mutation of Mkk3, suggesting involvement of the MKK3 signaling pathway in mediating the CO effects. Additionally, in vitro CO exposure markedly inhibited TGF-β1-induced expression of α-SMA, collagen, and fibronectin in renal proximal tubular epithelial cells. Our findings suggest that low-dose CO exerts protective effects, via the MKK3 pathway, to inhibit development of renal fibrosis in obstructive nephropathy.

scholarly journals Sorafenib Inhibits Renal Fibrosis Induced by Unilateral Ureteral Obstruction via Inhibition of Macrophage Infiltration

2016 ◽  
Vol 39 (5) ◽  
pp. 1837-1849 ◽  
Author(s):  
Wenting Ma ◽  
Le Tao ◽  
Xuefei Wang ◽  
Qinyi Liu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Cell Cancer ◽  
Unilateral Ureteral Obstruction ◽  
Macrophage Infiltration ◽  
Similar Distribution ◽  
Advanced Hepatocellular Carcinoma ◽  
Protective Effects ◽  
Sorafenib Treatment ◽  
Immunological Mechanisms

Aims: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. Methods: Mice underwent UUO followed by vehicle or sorafenib treatment. The expression of CD68, a macrophage marker, and the pro-inflammatory cytokines, MCP1 and CXCR3, were immunohistochemically analyzed. The involvement of macrophages in the formation of renal fibrosis was studied using confocal microscopy. Results: Renal histopathology improved in the UUO-sorafenib mice. Sorafenib notably suppressed TGF-β1-mediated renal fibrogenic effects. The mRNA and protein expressions of CD68, MCP1, and CXCR3 in the obstructed kidney were significantly decreased by sorafenib. Immunohistochemistry showed that CD68 and CXCR3 had a similar distribution, whereas MCP1 was observed predominantly in the tubular epithelial cells. Double immunofluorescence demonstrated that CD68-positive macrophages could co-localize with CXCR3. It also revealed that CXCR3 interacted with CXCL11 in the UUO mouse kidneys. Widespread adhesion of macrophages to myofibroblasts was markedly inhibited in UUO-sorafenib mouse kidneys. Conclusions: Taken together, the results indicated that sorafenib had protective effects against renal fibrosis; its mechanism of action was associated with inhibition of macrophage infiltration via the CXCR3/CXCL11 pathway. These data suggest the clinical potential of sorafenib for treatment of renal fibrosis and illustrate the immunological mechanisms underlying the protective effects of sorafenib.

scholarly journals Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction

2014 ◽  
Vol 8 (3) ◽  
pp. 727-730 ◽  
Author(s):  
YANG YAN ◽  
YUAN FENG ◽  
WEI LI ◽  
JIAN-PING CHE ◽  
GUANG-CHUN WANG ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Protective Effects

scholarly journals The farnesoid X receptor agonist EDP‐305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction

2019 ◽  
Vol 33 (6) ◽  
pp. 7103-7112 ◽  
Author(s):  
Shen Li ◽  
Sarani Ghoshal ◽  
Mozhdeh Sojoodi ◽  
Gunisha Arora ◽  
Ricard Masia ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Receptor Agonist ◽  
Unilateral Ureteral Obstruction ◽  
Farnesoid X Receptor

The antifibrotic and anti-inflammatory effects of icariin on the kidney in a unilateral ureteral obstruction mouse model

Phytomedicine ◽  
2019 ◽  
Vol 59 ◽  
pp. 152917 ◽  
Author(s):  
Hsin‐An Chen ◽  
Chang-Mu Chen ◽  
Siao-Syun Guan ◽  
Chih-Kang Chiang ◽  
Cheng-Tien Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Anti Inflammatory

scholarly journals NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Honglei Guo ◽  
Xiao Bi ◽  
Ping Zhou ◽  
Shijian Zhu ◽  
Wei Ding
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Mitochondrial Morphology ◽  
Glomerular Injury ◽  
Matrix Deposition

Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3−/− mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3−/− mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD.

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