Selective Targeting of Vascular Endothelial YAP Activity Blocks EndMT and Ameliorates Unilateral Ureteral Obstruction-Induced Kidney Fibrosis

2021 ◽  
Author(s):  
Yafeng Ren ◽  
Yuwei Zhang ◽  
Lu Wang ◽  
Fuqian He ◽  
Mengli Yan ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Vascular Endothelial ◽  
Kidney Fibrosis ◽  
Selective Targeting

scholarly journals Matrix Metalloproteinase-2 Knockout and Heterozygote Mice Are Protected from Hydronephrosis and Kidney Fibrosis after Unilateral Ureteral Obstruction

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143390 ◽  
Author(s):  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Sabine Leh ◽  
Frank Helle ◽  
Bjarne M. Iversen ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Matrix Metalloproteinase 2 ◽  
Kidney Fibrosis

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals Sphingosine Kinase-2 Deficiency Ameliorates Kidney Fibrosis by Up-Regulating Smad7 in a Mouse Model of Unilateral Ureteral Obstruction

2017 ◽  
Vol 187 (11) ◽  
pp. 2413-2429 ◽  
Author(s):  
Stephanie Schwalm ◽  
Sandra Beyer ◽  
Helena Frey ◽  
Riad Haceni ◽  
Georgios Grammatikos ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ureteral Obstruction ◽  
Sphingosine Kinase ◽  
Unilateral Ureteral Obstruction ◽  
Kidney Fibrosis ◽  
Sphingosine Kinase 2

scholarly journals Testosterone and Mast Cell Interactions in the Development of Kidney Fibrosis after Unilateral Ureteral Obstruction in Rats

2018 ◽  
Vol 41 (8) ◽  
pp. 1164-1169 ◽  
Author(s):  
Grasielle Lopes de Oliveira-Silva ◽  
Ingrid Beatriz de Melo Morais ◽  
Jéssica Fortunato-Silva ◽  
Marcela Maciel Palacio Alvarez ◽  
Nathane França-Silva ◽  
...  
Keyword(s):  
Mast Cell ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Cell Interactions ◽  
Kidney Fibrosis

scholarly journals Role of the high-affinity leukotriene B4 receptor signaling in fibrosis after unilateral ureteral obstruction in mice

2018 ◽  
Author(s):  
Mariko Kamata ◽  
Hideki Amano ◽  
Yoshiya Ito ◽  
Tomoe Fujita ◽  
Kanako Hosono ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Type I Collagen ◽  
Critical Role ◽  
Unilateral Ureteral Obstruction ◽  
Type I ◽  
Renal Tubules ◽  
Kidney Fibrosis ◽  
High Affinity

AbstractLeukotriene B4 (LTB4) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB4 receptor BLT1 during development of kidney fibrosis in wild-type (WT) mice and BLT1 knockout (BLT1-/-) mice with unilateral ureteral obstruction (UUO). We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB4, in the renal tubules of WT and BLT1-/- UUO mice. Accumulation of immunoreactive type I collagen in UUO kidneys of WT mice increased over time; however, the increase was less prominent in BLT1-/- mice. Accumulation of S100A4-positive fibroblasts also increased temporally in WT UUO kidneys, but was again less pronounced in those of BLT1-/- mice. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, also increased temporally in WT UUO and BLT1-/- kidneys, but to a lesser extent in the latter. Following LTB4 stimulation in vitro, macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1-/--BM→WT UUO kidneys than in WT-BM→WT kidneys. Thus, LTB4-BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis.

scholarly journals Centella asiatica Extract Attenuates Kidney Fibrosis Through Reducing Mesenchymal Transition and Inflammation in Ureteral Ligation Model in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Dwi Cahyani Ratna Sari ◽  
Santosa Budiharjo ◽  
Husnari Afifah ◽  
Destantry Jasmin ◽  
Orisativa Kokasih ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Area Fraction ◽  
Sham Operation ◽  
Tubular Injury ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
E Cadherin

Background: Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and is characterized by inflammation, mesenchymal transition with myofibroblast formation and epithelial to mesenchymal transition (EMT). Centella asiatia (CeA) is an herb that has a reno-protective effect. However, its mechanism of action in kidney fibrosis has not been elucidated.Aim: To elucidate the effect of CeA in amelioration of kidney fibrosis in a unilateral ureteral obstruction (UUO) model and focus on mesenchymal transition and inflammation.Methods: Unilateral ureteral obstruction was performed in male Swiss-background mice (age: 2–3 months, weight: 30–40 g, UUO group n = 6) to induce kidney fibrosis. Two doses of CeA extract with oral administration, 210 and 840 mg/kg body weight were added in UUO (U+C210 and U+C840 groups, each n = 6). The sham operation procedure was performed for the control group (SO, n = 6). The mice were euthanized at day-14 after operation. Tubular injury and interstitial fibrosis area fractions in kidney tissues of the mice were quantified based on periodic acid-Schiff (PAS) and Sirius Red (SR) staining. Immunostaining was performed for examination of fibroblast (PDGFR-β), myofibroblast (α-SMA), Monocyte Chemoattractant Protein-1 (MCP-1) and macrophage (CD68), meanwhile double immunofluorescence was performed with PDGFR-β and α-SMA. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to examine mRNA expression of TGF-β, Collagen-1, Snail, E-cadherin, vimentin, fibroblast-specific protein 1 (FSP-1), CD68, toll-like receptor 4 (TLR4), and MCP-1.Results: We observed a significantly higher interstitial fibrosis area fraction and tubular injury (p < 0.001) with fibroblast expansion and myofibroblast formation in the UUO group than in the SO group. These findings were associated with higher mRNA expression of TGF-β, Collagen-1, Snail, vimentin, FSP-1, CD68, TLR4, and MCP-1 and lower mRNA expression of E-cadherin. The U+C840 group had a significantly lower tubular injury score and interstitial fibrosis area fraction, which associated with downregulation of mRNA expression of TGF-β, Collagen-1, Snail, vimentin, FSP-1, CD68, TLR4, and MCP-1, with upregulation of mRNA expression of E-cadherin. Immunostaining observation revealed the U+C840 group demonstrated reduction of macrophage infiltration and myofibroblast expansion.Conclusion: CeA treatment with dose-dependently ameliorates mesenchymal transition and inflammation in kidney fibrosis in mice.

scholarly journals Autophagy Regulates TGF-β Expression and Suppresses Kidney Fibrosis Induced by Unilateral Ureteral Obstruction

2014 ◽  
Vol 25 (12) ◽  
pp. 2835-2846 ◽  
Author(s):  
Yan Ding ◽  
Sung ll Kim ◽  
So-Young Lee ◽  
Ja Kun Koo ◽  
Zhibo Wang ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Kidney Fibrosis

scholarly journals Unilateral Ureteral Obstruction as a Model of Kidney Fibrosis and Increasing of Systolic Blood Pressure in Mice

2019 ◽  
Vol 2 (3) ◽  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Kidney Fibrosis ◽  
End Stage

Background: Obstructive nephropathy can lead to progressive and permanent loss of kidney function characterized by interstitial inflammation and tubulointerstitial fibrosis. Tubulointerstitial fibrosis presents as the end result of various kidney injuries in general and can cause chronic kidney disease (CKD), which can progress to end-stage kidney disease and hypertension. Objective: This study aimed to determine the effectiveness of unilateral ureteral obstruction (UUO) as a model of renal fibrosis and hypertension. Method: Sixteen male Rattus norvegicus mice (150-200 g) were divided into control groups and UUO by ureteral ligation, eight mice each. The systolic blood pressure (SBP) were measured every seven days. After 30 days the animals were dissected to analyze the changes in renal interstitial fibrosis. Statistical analysis was carried out by unpaired t test or alternative test. Results: There was a significant increase in interstitial fibrosis in the UUO rat group [1% (0% - 5%) vs. 75% (20% - ­90%), p <0.001] and SBP [85.38 ± 1.69 mmHg vs 144.75 ± 4.27 mmHg, p <0.001]. Conclusion: UUO can be used as a model of fibrosis and hypertension, which can be used as the basis for the development of anti-fibrotic and anti-hypertensive drugs.

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