scholarly journals Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis.

1997 ◽  
Vol 99 (2) ◽  
pp. 194-199 ◽  
Author(s):  
J L Brasier ◽  
E P Henske
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Loss Of Function ◽  
Polycystic Kidney ◽  
Function Model ◽  
Cyst Cells ◽  
Chromosome 16P13

scholarly journals A Loss-of-Function Model for Cystogenesis in Human Autosomal Dominant Polycystic Kidney Disease Type 2

1999 ◽  
Vol 65 (2) ◽  
pp. 345-352 ◽  
Author(s):  
Roser Torra ◽  
Cèlia Badenas ◽  
José L. San Millán ◽  
Laureano Pérez-Oller ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Disease Type ◽  
Loss Of Function ◽  
Polycystic Kidney ◽  
Function Model ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Gender-Dependent Phenotype in Polycystic Kidney Disease Is Determined by Differential Intracellular Ca2+ Signals

2021 ◽  
Vol 22 (11) ◽  
pp. 6019
Author(s):  
Khaoula Talbi ◽  
Inês Cabrita ◽  
Rainer Schreiber ◽  
Karl Kunzelmann
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Collecting Duct ◽  
Primary Cells ◽  
Loss Of Function ◽  
Polycystic Kidney ◽  
Chloride Currents ◽  
Duct Cells ◽  
Collecting Duct Cells

Autosomal dominant polycystic kidney disease (ADPKD) is caused by loss of function of PKD1 (polycystin 1) or PKD2 (polycystin 2). The Ca2+-activated Cl− channel TMEM16A has a central role in ADPKD. Expression and function of TMEM16A is upregulated in ADPKD which causes enhanced intracellular Ca2+ signaling, cell proliferation, and ion secretion. We analyzed kidneys from Pkd1 knockout mice and found a more pronounced phenotype in males compared to females, despite similar levels of expression for renal tubular TMEM16A. Cell proliferation, which is known to be enhanced with loss of Pkd1−/−, was larger in male when compared to female Pkd1−/− cells. This was paralleled by higher basal intracellular Ca2+ concentrations in primary renal epithelial cells isolated from Pkd1−/− males. The results suggest enhanced intracellular Ca2+ levels contributing to augmented cell proliferation and cyst development in male kidneys. Enhanced resting Ca2+ also caused larger basal chloride currents in male primary cells, as detected in patch clamp recordings. Incubation of mouse primary cells, mCCDcl1 collecting duct cells or M1 collecting duct cells with dihydrotestosterone (DHT) enhanced basal Ca2+ levels and increased basal and ATP-stimulated TMEM16A chloride currents. Taken together, the more severe cystic phenotype in males is likely to be caused by enhanced cell proliferation, possibly due to enhanced basal and ATP-induced intracellular Ca2+ levels, leading to enhanced TMEM16A currents. Augmented Ca2+ signaling is possibly due to enhanced expression of Ca2+ transporting/regulating proteins.

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 Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 42 ◽  
Author(s):  
Li-Fang Chou ◽  
Ya-Lien Cheng ◽  
Chun-Yih Hsieh ◽  
Chan-Yu Lin ◽  
Huang-Yu Yang ◽  
...  
Keyword(s):  
Drinking Water ◽  
Kidney Disease ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Pure Water ◽  
Immunohistochemical Analysis ◽  
Positive Staining ◽  
Wild Type ◽  
Polycystic Kidney

Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treatment reduces renal cyst formation in a Pkd1-hypomorphic mouse model. Pkd1 miRNA transgenic (Pkd1 miR Tg) mice and wild-type littermates were given drinking water supplemented with 2% trehalose from postnatal day 35 to postnatal day 91. The control groups received pure water or 2% sucrose for the control of hyperosmolarity. The effect on kidney weights, cystic indices, renal function, cell proliferation, and autophagic activities was determined. We found that Pkd1 miR Tg mice had a significantly lower renal mRNA expression of autophagy-related genes, including atg5, atg12, ulk1, beclin1, and p62, compared with wild-type control mice. Furthermore, immunohistochemical analysis showed that cystic lining cells had strong positive staining for the p62 protein, indicating impaired degradation of the protein by the autophagy-lysosome pathway. However, trehalose treatment did not improve reduced autophagy activities, nor did it reduce relative kidney weights, plasma blood urea nitrogen levels, or cystatin C levels in Pkd1 miR Tg mice. Histomorphological analysis revealed no significant differences in the renal cyst index, fibrosis score, or proliferative score among trehalose-, sucrose-, and water-treated groups. Our results demonstrate that adding trehalose to drinking water does not modulate autophagy activities and renal cystogenesis in Pkd1-deficient mice, suggesting that an oral supplement of trehalose may not affect the progression of ADPKD.

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 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
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