scholarly journals Obacunone Retards Renal Cyst Development in Autosomal Dominant Polycystic Kidney Disease by Activating NRF2

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 38
Author(s):  
Zhiwei Qiu ◽  
Jinzhao He ◽  
Guangying Shao ◽  
Jiaqi Hu ◽  
Xiaowei Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Renal Cyst ◽  
Renal Diseases ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Development

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

scholarly journals Gas-forming infection in a renal cyst of a patient with autosomal dominant polycystic kidney disease

2005 ◽  
Vol 21 (2) ◽  
pp. 555-556 ◽  
Author(s):  
Reha Erkoc ◽  
Hayriye Sayarlioglu ◽  
Kadir Ceylan ◽  
Ekrem Dogan ◽  
Pinar Sonat Kara
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Renal Cyst ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Renal cyst fluid proteomics in autosomal dominant polycystic kidney disease (ADPKD)

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Xianyin Lai ◽  
Robert L. Bacallao ◽  
Bonnie L. Blazer‐Yost ◽  
David Hong ◽  
Stephen B. Mason ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Renal Cyst ◽  
Cyst Fluid ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Is There a Role of ADAMTS-1 in Cyst Development in Autosomal Dominant Polycystic Kidney Disease?

2021 ◽  
Vol 30 (1) ◽  
pp. 25-29
Author(s):  
Suleyman Karakose ◽  
◽  
Pervin Ozkan Kurtgoz ◽  
Cigdem Damla Deniz ◽  
Edip Erkus ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Development

Autosomal dominant polycystic kidney disease in absence of renal cyst formation illustrates genetic interaction between WT1 and PKD1

2020 ◽  
pp. jmedgenet-2019-106633
Author(s):  
Johannes Münch ◽  
Karin M Kirschner ◽  
Hendrik Schlee ◽  
Cornelia Kraus ◽  
Ria Schönauer ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Genetic Interaction ◽  
Renal Cyst ◽  
Family Members ◽  
Cyst Formation ◽  
Polycystic Kidney ◽  
Pathogenic Variants ◽  
Autosomal Dominant Polycystic Kidney

PurposeAutosomal dominant polycystic kidney disease (ADPKD), caused by pathogenic variants of either PKD1 or PKD2, is characterised by wide interfamilial and intrafamilial phenotypic variability. This study aimed to determine the molecular basis of marked clinical variability in ADPKD family members and sought to analyse whether alterations of WT1 (Wilms tumour 1), encoding a regulator of gene expression, may have an impact on renal cyst formation.MethodsADPKD family members underwent clinical and molecular evaluation. Functionally, Pkd1 mRNA and protein expression upon Wt1 knockdown was evaluated in mouse embryonic kidneys and mesonephric M15 cells.ResultsBy renal gene panel analysis, we identified two pathogenic variants in an individual with maternal history of ADPKD, however, without cystic kidneys but polycystic liver disease: a known PKD1 missense variant (c.8311G>A, p.Glu2771Lys) and a known de novo WT1 splice site variant (c.1432+4C>T). The latter was previously associated with imbalanced +/−KTS isoform ratio of WT1. In ex vivo organ cultures from mouse embryonic kidneys, Wt1 knockdown resulted in decreased Pkd1 expression on mRNA and protein level.ConclusionWhile the role of WT1 in glomerulopathies has been well established, this report by illustrating genetic interaction with PKD1 proposes WT1 as potential modifier in ADPKD.

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.

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