scholarly journals Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease

2016 ◽  
Vol 89 (6) ◽  
pp. 1307-1323 ◽  
Author(s):  
Dongmei Lu ◽  
Alysha Rauhauser ◽  
Binghua Li ◽  
Chongyu Ren ◽  
Kayla McEnery ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Epithelial Cell ◽  
Mouse Model ◽  
Cell Senescence ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Kidney Epithelial Cell ◽  
Cyst Growth

scholarly journals Targeted exon skipping of a CEP290 mutation rescues Joubert syndrome phenotypes in vitro and in a murine model

2018 ◽  
Vol 115 (49) ◽  
pp. 12489-12494 ◽  
Author(s):  
Simon A. Ramsbottom ◽  
Elisa Molinari ◽  
Shalabh Srivastava ◽  
Flora Silberman ◽  
Charline Henry ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Exon Skipping ◽  
Joubert Syndrome ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Kidney Cells ◽  
Promising Therapeutic Approach

Genetic treatments of renal ciliopathies leading to cystic kidney disease would provide a real advance in current therapies. Mutations in CEP290 underlie a ciliopathy called Joubert syndrome (JBTS). Human disease phenotypes include cerebral, retinal, and renal disease, which typically progresses to end stage renal failure (ESRF) within the first two decades of life. While currently incurable, there is often a period of years between diagnosis and ESRF that provides a potential window for therapeutic intervention. By studying patient biopsies, patient-derived kidney cells, and a mouse model, we identify abnormal elongation of primary cilia as a key pathophysiological feature of CEP290-associated JBTS and show that antisense oligonucleotide (ASO)-induced splicing of the mutated exon (41, G1890*) restores protein expression in patient cells. We demonstrate that ASO-induced splicing leading to exon skipping is tolerated, resulting in correct localization of CEP290 protein to the ciliary transition zone, and restoration of normal cilia length in patient kidney cells. Using a gene trap Cep290 mouse model of JBTS, we show that systemic ASO treatment can reduce the cystic burden of diseased kidneys in vivo. These findings indicate that ASO treatment may represent a promising therapeutic approach for kidney disease in CEP290-associated ciliopathy syndromes.

scholarly journals Effect of dimethyl fumarate on renal disease progression in a genetic ortholog of nephronophthisis

2018 ◽  
Vol 243 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Oliver Oey ◽  
Padmashree Rao ◽  
Magdalena Luciuk ◽  
Carly Mannix ◽  
Natasha M Rogers ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Dimethyl Fumarate ◽  
Macrophage Infiltration ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Nuclear Factor ◽  
Polycystic Kidney ◽  
Cyst Growth

Dimethyl fumarate is an FDA-approved oral immunomodulatory drug with anti-inflammatory properties that induces the upregulation of the anti-oxidant transcription factor, nuclear factor erythroid-derived factor 2. The aim of this study was to determine the efficacy of dimethyl fumarate on interstitial inflammation and renal cyst growth in a preclinical model of nephronophthisis. Four-week-old female Lewis polycystic kidney disease (a genetic ortholog of human nephronophthisis-9) rats received vehicle (V), 10 mg/kg (D10) or 30 mg/kg (D30) ( n = 8–9 each) dimethyl fumarate in drinking water for eight weeks. Age-matched Lewis control rats were also studied ( n = 4 each). Nuclear factor erythroid-derived factor 2 was quantified by whole-slide image analysis of kidney sections. Renal nuclear factor erythroid-derived factor 2 activation was partially reduced in vehicle-treated Lewis polycystic kidney disease rats compared to Lewis control (21.4 ± 1.7 vs. 27.0 ± 1.6%, mean ± SD; P < 0.01). Dimethyl fumarate upregulated nuclear factor erythroid-derived factor 2 in both Lewis Polycystic Kidney Disease (D10: 35.9 ± 3.8; D30: 33.6 ± 3.4%) and Lewis rats (D30: 34.4 ± 1.3%) compared to vehicle-treated rats ( P < 0.05). Dimethyl fumarate significantly reduced CD68+ cell accumulation in Lewis polycystic kidney disease rats (V: 31.7 ± 2.4; D10: 23.0 ± 1.1; D30: 21.5 ± 1.9; P < 0.05). In Lewis polycystic kidney disease rats, dimethyl fumarate did not alter the progression of kidney enlargement (V: 6.4 ± 1.6; D10: 6.9 ± 1.2; D30: 7.3 ± 1.3%) and the percentage cystic index (V: 59.1 ± 2.7; D10: 55.7 ± 3.5; D30: 58.4 ± 2.9%). Renal dysfunction, as determined by the serum creatinine (Lewis + V: 26 ± 4 vs. LPK + V: 60 ± 25 P < 0.01; LPK + D10: 47 ± 7; LPK + D30: 47 ± 9 µmol/L), and proteinuria were also unaffected by dimethyl fumarate treatment. In conclusion, the upregulation of nuclear factor erythroid-derived factor 2 by dimethyl fumarate reduced renal macrophage infiltration in nephronophthisis without adverse effects, suggesting that it could potentially be used in combination with other therapies that reduce the rate of renal cyst growth. Impact statement This is the first study to investigate the effects of dimethyl fumarate in a model of cystic kidney disease. The study assessed the therapeutic efficacy of dimethyl fumarate in upregulating renal nuclear factor erythroid-derived factor 2 expression, reducing macrophage accumulation and cyst progression in a Lewis polycystic kidney disease rat model. This study demonstrates that dimethyl fumarate significantly upregulated renal nuclear factor erythroid-derived factor 2 expression and attenuates renal macrophage infiltration, but had no effect on renal cyst progression, cardiac enlargement, and improving renal function.

Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease

2014 ◽  
Vol 88 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Chaowalit Yuajit ◽  
Chatchai Muanprasat ◽  
Anna-Rachel Gallagher ◽  
Sorin V. Fedeles ◽  
Suticha Kittayaruksakul ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Epithelial Cell ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Epithelial Cell Proliferation ◽  
Polycystic Kidney ◽  
Cyst Growth

scholarly journals Caffeine Accelerates Cystic Kidney Disease in a Pkd1-Deficient Mouse Model

2019 ◽  
Vol 52 (5) ◽  
pp. 1061-1074 ◽  
Author(s):  
Renata Meca ◽  
◽  
Bruno E. Balbo ◽  
Milene Subtil Ormanji ◽  
Jonathan M. Fonseca ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Deficient Mouse

Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review

1990 ◽  
Vol 9 (6) ◽  
pp. 397-401 ◽  
Author(s):  
K.N. Woodward
Keyword(s):  
Kidney Disease ◽  
Human Health ◽  
Phthalate Esters ◽  
Renal Cysts ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Peroxisome Proliferation ◽  
Peroxisome Proliferators ◽  
Prolonged Administration ◽  
Route Of Exposure

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4 More studies are needed on the mechanism of renal cystogenesis.

Robinow syndrome: report of two patients with cystic kidney disease

2008 ◽  
Vol 37 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Lynn Wiens ◽  
D. K. Strickland ◽  
Barbara Sniffen ◽  
Bradley A. Warady
Keyword(s):  
Kidney Disease ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Robinow Syndrome ◽  
Syndrome Report
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