Interferon-γ Improves Renal Interstitial Fibrosis and Decreases Intrarenal Vascular Resistance of Hydronephrosis in an Animal Model

Yao, Yi; Zhang, Jie; Tan, Daqing; Chen, Xiaoyi; Ye, Da-Fu; Peng, Jianping; Li, Jingtao; Zheng, Yang; Li, Fang; Li, Youkong; Fan, Min

doi:10.1016/j.urology.2010.10.015

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…Numerous papers that focus on the molecular biological mechanisms associated with renal interstitial fibrosis due to obstructive nephropathy have been recently published [ 10 , 13 , 14 ]. However, there is limited radiological research on renal interstitial fibrosis in the case of hydronephrosis.…”

Section: Discussionmentioning

confidence: 99%

Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

et al. 2014

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Purpose:To measure shear wave velocities (SWVs) by acoustic radiation force impulse (ARFI) ultrasound elastography in normal kidneys and in hydronephrotic kidneys in young children and to compare SWVs between the hydronephrosis grades.Methods:This study was approved by an institutional review board, and informed consent was obtained from the parents of all the children included. Children under the age of 24 months were prospectively enrolled. Hydronephrosis grade was evaluated on ultrasonography, and three valid ARFI measurements were attempted using a high-frequency transducer for both kidneys. Hydronephrosis was graded from 0 to 4, and high-grade hydronephrosis was defined as grades 3 and 4.Results:Fifty-one children underwent ARFI measurements, and three valid measurements for both kidneys were obtained in 96% (49/51) of the patients. Nineteen children (38.8%) had no hydronephrosis. Twenty-three children (46.9%) had unilateral hydronephrosis, and seven children (14.3%) had bilateral hydronephrosis. Seven children had ureteropelvic junction obstruction (UPJO). Median SWVs in kidneys with high-grade hydronephrosis (2.02 m/sec) were higher than those in normal kidneys (1.75 m/sec; P=0.027). However, the presence of UPJO did not influence the median SWVs in hydronephrotic kidneys (P=0.362).Conclusion:Obtaining ARFI measurements of the kidney is feasible in young children with median SWVs of 1.75 m/sec in normal kidneys. Median SWVs increased in high-grade hydronephrotic kidneys but were not different between hydronephrotic kidneys with and without UPJO.

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Section: Discussionmentioning

confidence: 99%

Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

et al. 2014

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“…In addition to its proinflammatory effects, IFN‐γ has prominent antiproliferative and antifibrotic effects (19, 20). IFN‐γ inhibits fibroblast activation and proliferation and also reduces collagen synthesis (18, 20, 21), thereby making it an interesting molecule for therapeutic use to target fibrosis. However, the short half‐life and undesirable systemic side effects clearly limit clinical use of IFN‐γ (22, 23).…”

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confidence: 99%

Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

et al. 2014

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Renal fibrosis leads to end-stage renal disease demanding renal replacement therapy because no adequate treatment exists. IFN-g is an antifibrotic cytokine that may attenuate renal fibrosis. Systemically administered IFN-g causes side effects that may be prevented by specific drug targeting. Interstitial myofibroblasts are the effector cells in renal fibrogenesis. Here, we tested the hypothesis that cell-specific delivery of IFN-g to plateletderived growth factor receptor b (PDGFRb)-expressing myofibroblasts attenuates fibrosis in an obstructive nephropathy [unilateral ureteral obstruction (UUO)] mouse model. PEGylated IFN-g conjugated to PDGFRbrecognizing peptide [(PPB)-polyethylene glycol (PEG)-IFN-g] was tested in vitro and in vivo for antifibrotic properties and compared with free IFN-g. PDGFRb expression was >3-fold increased (P < 0.05) in mouse fibrotic UUO kidneys and colocalized with a-smooth muscle actin-positive (SMA + ) myofibroblasts.

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“…In addition to its pro-inflammatory effects, IFNγ has prominent anti-fibrotic effects. IFNγ is able to inhibit fibroblast activation and proliferation, and also reduces ECM synthesis ( Lee et al, 2013 ; Oldroyd et al, 1999 ; Strutz et al, 2000 ; Weng et al, 2005 ; Yao et al, 2011 ). These properties make IFNγ a potential molecule for therapeutic use to target fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo

Poosti

Pham

Oosterhuis

et al. 2015

Disease Models &Amp; Mechanisms

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Renal fibrosis is a serious clinical problem resulting in the greatest need for renal replacement therapy. No adequate preventive or curative therapy is available that could be clinically used to target renal fibrosis specifically. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, we here evaluated a precision-cut kidney slice (PCKS) model as a new, multicellular ex vivo model to study the development of fibrosis and its prevention using anti-fibrotic compounds. Precision-cut slices (200-300 μm thickness) were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGFβ1 (5 ng/ml) for 48 h in the presence or absence of the anti-fibrotic cytokine IFNγ (1 µg/ml) or an IFNγ conjugate targeted to PDGFRβ (PPB-PEG-IFNγ). Following culture, tissue viability (ATP-content) and expression of α-SMA, fibronectin, collagen I and collagen III were determined using real-time PCR and immunohistochemistry. Slices remained viable up to 72 h of incubation, and no significant effects of TGFβ1 and IFNγ on viability were observed. TGFβ1 markedly increased α-SMA, fibronectin and collagen I mRNA and protein expression levels. IFNγ and PPB-PEG-IFNγ significantly reduced TGFβ1-induced fibronectin, collagen I and collagen III mRNA expression, which was confirmed by immunohistochemistry. The PKCS model is a novel tool to test the pathophysiology of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. A major advantage of the slice model is that it can be used not only for animal but also for (fibrotic) human kidney tissue.

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Interferon-γ Improves Renal Interstitial Fibrosis and Decreases Intrarenal Vascular Resistance of Hydronephrosis in an Animal Model

Cited by 12 publications

References 28 publications

Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo

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