scholarly journals Assessment of Renal Fibrosis with Diffusion-weighted MR Imaging: Study with Murine Model of Unilateral Ureteral Obstruction

Radiology ◽  
2010 ◽  
Vol 255 (3) ◽  
pp. 772-780 ◽  
Author(s):  
Osamu Togao ◽  
Shigehiro Doi ◽  
Makoto Kuro-o ◽  
Takao Masaki ◽  
Noriaki Yorioka ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Murine Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Imaging Study ◽  
Unilateral Ureteral Obstruction ◽  
Diffusion Weighted

scholarly journals Deletion of Akt1 Promotes Kidney Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Il Young Kim ◽  
Min Young Lee ◽  
Mi Wha Park ◽  
Eun Young Seong ◽  
Dong Won Lee ◽  
...  
Keyword(s):  
Murine Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Type I ◽  
Wild Type ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Hk2 Cells

We investigated the role of Akt1, one of the three isoforms of Akt, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). We subjected wild type and Akt1−/− mice to UUO. The Akt1 gene was silenced in vitro using short hairpin RNA delivered via a lentiviral vector in human proximal tubular cells (HK2 cells) and kidney fibroblasts (NRK-49F cells). The obstructive kidneys of Akt1−/− mice showed more severe tubulointerstitial fibrosis than those of wild type mice. The expression of fibronectin and type I collagen was significantly increased in obstructed kidneys of Akt1−/− mice compared to those of wild type mice. The important finding was that the expression of transforming growth factor β1 (TGFβ1) was significantly increased in the Akt1−/− mice compared to the wild type mice. The knockdown of Akt1 enhanced the expression of TGFβ1 in HK2 cells. Interestingly, the upregulation of TGFβ1 due to genetic knockdown of Akt1 was associated with activation of signal transducer and activator of transcript 3 (STAT3) independently of the Smad pathway in NRK-49F and HK2 cells. Immunohistochemical staining also showed that expression of phosphorylated STAT3 was more increased in Akt1−/− mice than in wild type mice after UUO. Additionally, the deletion of Akt1 led to apoptosis of the renal tubular cells in both in vivo and in vitro studies. Conclusively, these results suggest that the deletion of Akt1 may contribute to renal fibrosis via induction of the TGFβ1/STAT3 pathway in a murine model of UUO.

Intravoxel incoherent imaging of renal fibrosis induced in a murine model of unilateral ureteral obstruction

2015 ◽  
Vol 33 (10) ◽  
pp. 1324-1328 ◽  
Author(s):  
Tiffany Hennedige ◽  
Tong San Koh ◽  
Septian Hartono ◽  
Yet Yen Yan ◽  
In Chin Song ◽  
...  
Keyword(s):  
Murine Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Incoherent Imaging

scholarly journals P0734THE DELETION OF AKT1 PROMOTES THE RENAL FIBROSIS IN THE MURINE MODEL OF UNILATERAL URETERAL OBSTRUCTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Il Young Kim ◽  
Byung Min Ye ◽  
Min Jeong Kim ◽  
Dong Won Lee ◽  
Soo Bong Lee ◽  
...  
Keyword(s):  
Western Blot ◽  
Murine Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Caspase 3 ◽  
Unilateral Ureteral Obstruction ◽  
Wild Type ◽  
Immunohistochemical Stain ◽  
In The Wild ◽  
Hk2 Cells

Abstract Background and Aims Previous studies have found the increased Akt activity in experimental renal fibrosis. We investigated the role of Akt1, one of the three Akt isoforms, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). Method In vivo, we subjected the wild type and Akt1−/− mice to UUO. In vitro, gene silencing of Akt1 was achieved using the short hairpin RNA delivered by the lentiviral vector in immortalized human proximal tubular cells (HK2 cells) and rat kidney fibroblasts (NRK-49F cells). Results In immunohistochemical stain, the expression of Akt1 was significantly higher in obstructed kidneys of wild type mice compared with control sham kidneys and increased gradually as UUO progressed. The fibronectin, type I collagen, and heat shock protein 47 (HSP47) were markedly more expressed in obstructed kidneys of Akt1−/− mice than in those of the wild type mice. Transforming growth factor β1 (TGFβ1) was highly induced within 1 day of UUO in obstructed kidneys of Akt1−/− mice and the expression of TGFβ1 was significantly higher in the Akt1−/− mice than in the wild type mice as UUO progressed. Western blot showed that silencing of Akt1 increased the expression of TGFβ1, which was enhanced by angiotensin II stimulation in HK2 cells, but not in NRK-49F cells. Immunohistochemical stain demonstrated that the expression of cleaved caspase-3 in renal tubules was significantly higher in the Akt1−/− mice than in the wild type mice. Western blot showed that silencing of Akt1 increased the expression of cleaved caspase-3 in HK2 cells, but not in NRK-49F cells. Conclusion Our findings suggest that the deletion of Akt1 might contribute to tubulointerstitial fibrosis and tubular apoptosis via TGFβ1 induction. We also showed that TGFβ1 upregulation by genetic deletion of Akt1 is associated with activation of STAT3 independently of the TGFβ1/Smad signaling pathway.

scholarly journals SAMP1/Sku as a Murine Model for Tubulointerstitial Nephritis: a Study Using Unilateral Ureteral Obstruction

2005 ◽  
Vol 54 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Akira YABUKI ◽  
Michie MAEDA ◽  
Mitsuharu MATSUMOTO ◽  
Ryozo KAMIMURA ◽  
Taku MASUYAMA ◽  
...  
Keyword(s):  
Murine Model ◽  
Ureteral Obstruction ◽  
Tubulointerstitial Nephritis ◽  
Unilateral Ureteral Obstruction

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.

scholarly journals The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Nephron Extra ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Masashi Nishida ◽  
Yasuko Okumura ◽  
Tatsujiro Oka ◽  
Kentaro Toiyama ◽  
Seiichiro Ozawa ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Angiotensin Receptor Blocker ◽  
Unilateral Ureteral Obstruction ◽  
Receptor Blocker ◽  
Angiotensin Receptor

scholarly journals L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110365 ◽  
Author(s):  
Bárbara Oujo ◽  
José M. Muñoz-Félix ◽  
Miguel Arévalo ◽  
Elena Núñez-Gómez ◽  
Lucía Pérez-Roque ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction

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.

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