scholarly journals Novel Potential Application of Chitosan Oligosaccharide for Attenuation of Renal Cyst Growth in the Treatment of Polycystic Kidney Disease

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5589 ◽  
Author(s):  
Nutthapoom Pathomthongtaweechai ◽  
Sunhapas Soodvilai ◽  
Rath Pichyangkura ◽  
Chatchai Muanprasat
Keyword(s):  
Protein Kinase ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Kidney Diseases ◽  
Biological Activities ◽  
Genetic Disorder ◽  
Chitosan Oligosaccharide ◽  
Polycystic Kidney ◽  
Cyst Growth

Chitosan oligosaccharide (COS), a natural polymer derived from chitosan, exerts several biological activities including anti-inflammation, anti-tumor, anti-metabolic syndrome, and drug delivery enhancer. Since COS is vastly distributed to kidney and eliminated in urine, it may have a potential advantage as the therapeutics of kidney diseases. Polycystic kidney disease (PKD) is a common genetic disorder characterized by multiple fluid-filled cysts, replacing normal renal parenchyma and leading to impaired renal function and end-stage renal disease (ESRD). The effective treatment for PKD still needs to be further elucidated. Interestingly, AMP-activated protein kinase (AMPK) has been proposed as a drug target for PKD. This study aimed to investigate the effect of COS on renal cyst enlargement and its underlying mechanisms. We found that COS at the concentrations of 50 and 100 µg/mL decreased renal cyst growth without cytotoxicity, as measured by MTT assay. Immunoblotting analysis showed that COS at 100 µg/mL activated AMPK, and this effect was abolished by STO-609, a calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) inhibitor. Moreover, COS elevated the level of intracellular calcium. These results suggest that COS inhibits cyst progression by activation of AMPK via CaMKKβ. Therefore, COS may hold the potential for pharmaceutical application in PKD.

scholarly journals Chronic exercise protects against the progression of renal cyst growth and dysfunction in rats with polycystic kidney disease

2021 ◽  
Author(s):  
Jiahe Qiu ◽  
Yoichi Sato ◽  
Lusi Xu ◽  
Takahiro Miura ◽  
Masahiro Kohzuki ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Genetic Disorder ◽  
Exercise Group ◽  
Chronic Exercise ◽  
Polycystic Kidney ◽  
Camp Content ◽  
Fatty Acid Binding ◽  
Cyst Growth

AbstractIntroductionPolycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. The effects of chronic exercise on the progression of PKD were investigated in a polycystic kidney (PCK) rat model.MethodsSix-week-old male PCK rats were divided into a sedentary group and an exercise group. The exercise group underwent forced treadmill exercise for 12 weeks (28 m/min, 60 min/day, 5 days/week). After 12 weeks, kidney function and histology were examined, protein expressions were analyzed, and signaling cascades of PKD were examined.ResultsChronic exercise reduced the excretion of urinary protein, liver-type fatty acid-binding protein, plasma creatinine, urea nitrogen, and increased plasma irisin and urinary arginine vasopressin (AVP) excretion. Chronic exercise also slowed renal cyst growth, glomerular damage, and interstitial fibrosis, and led to reduced Ki-67 expression. Chronic exercise had no effect on cAMP content but decreased the renal expression of B-Raf and reduced the phosphorylation of extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and S6.ConclusionChronic exercise slows renal cyst growth and damage in PCK rats, despite increasing AVP, with down-regulation of the cAMP/B-Raf/ERK and mTOR/S6 pathways in the kidney of PCK rats.

scholarly journals Signal transducer and activator of transcription-6 (STAT6) inhibition suppresses renal cyst growth in polycystic kidney disease

2011 ◽  
Vol 108 (44) ◽  
pp. 18067-18072 ◽  
Author(s):  
E. E. Olsan ◽  
S. Mukherjee ◽  
B. Wulkersdorfer ◽  
J. M. Shillingford ◽  
A. J. Giovannone ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Signal Transducer ◽  
Polycystic Kidney ◽  
Cyst Growth

scholarly journals Autophagy induction promotes renal cyst growth in polycystic kidney disease

EBioMedicine ◽  
2020 ◽  
Vol 60 ◽  
pp. 102986
Author(s):  
Eun Ji Lee ◽  
Je Yeong Ko ◽  
Sumin Oh ◽  
Jaehee Jun ◽  
Hyowon Mun ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Polycystic Kidney ◽  
Autophagy Induction ◽  
Cyst Growth

scholarly journals Regression of Peritubular Capillaries Coincides with Angiogenesis and Renal Cyst Growth in Experimental Polycystic Kidney Disease

2020 ◽  
Vol Volume 13 ◽  
pp. 53-64 ◽  
Author(s):  
Kristal O'Brien ◽  
Sayanthooran Saravanabavan ◽  
Jennifer QJ Zhang ◽  
Annette TY Wong ◽  
Alexandra Munt ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Polycystic Kidney ◽  
Peritubular Capillaries ◽  
Cyst Growth

Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a polycystic kidney disease mouse model

2018 ◽  
Vol 9 (1) ◽  
pp. 389-396 ◽  
Author(s):  
Yangyang Zhu ◽  
Tian Teng ◽  
Hu Wang ◽  
Hao Guo ◽  
Lei Du ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Renal Cyst ◽  
Monogenic Disease ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Growth

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney.

scholarly journals Chronic Exercise Protects against the Progression of Renal Cyst Growth and Dysfunction in Rats with Polycystic Kidney Disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jiahe Qiu ◽  
Yoichi Sato ◽  
Lusi Xu ◽  
Takahiro Miura ◽  
Masahiro Kohzuki ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Chronic Exercise ◽  
Polycystic Kidney ◽  
Cyst Growth

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.

scholarly journals In vitro 3D phenotypic drug screen identifies celastrol as an effective in vivo inhibitor of polycystic kidney disease

2019 ◽  
Vol 12 (8) ◽  
pp. 644-653 ◽  
Author(s):  
Tijmen H Booij ◽  
Wouter N Leonhard ◽  
Hester Bange ◽  
Kuan Yan ◽  
Michiel Fokkelman ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Genetic Disorder ◽  
Screening Method ◽  
Renal Cysts ◽  
Cyst Formation ◽  
Polycystic Kidney ◽  
Cyst Growth

Abstract Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signaling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium Wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1lox,lox mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function.

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