• BMB Reports
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• v.46 no.2
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• pp.73-79
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• 2013

Polycystic kidney disease (PKD) is a common hereditary disorder which is characterized by fluid-filled cysts in the kidney. Mutation in either PKD1, encoding polycystin-1 (PC1), or PKD2, encoding polycystin-2 (PC2), are causative genes of PKD. Recent studies indicate that renal cilia, known as mechanosensors, detecting flow stimulation through renal tubules, have a critical function in maintaining homeostasis of renal epithelial cells. Because most proteins related to PKD are localized to renal cilia or have a function in ciliogenesis. PC1/PC2 heterodimer is localized to the cilia, playing a role in calcium channels. Also, disruptions of ciliary proteins, except for PC1 and PC2, could be involved in the induction of polycystic kidney disease. Based on these findings, various PKD mice models were produced to understand the roles of primary cilia defects in renal cyst formation. In this review, we will describe the general role of cilia in renal epithelial cells, and the relationship between ciliary defects and PKD. We also discuss mouse models of PKD related to ciliary defects based on recent studies.

• BMB Reports
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• v.44 no.6
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• pp.359-368
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• 2011

Polycystic kidney disease (PKD) is a common genetic disorder in which extensive epithelial-lined cysts develop in the kidneys. In previous studies, abnormalities of polycystin protein and its interacting proteins, as well as primary cilia, have been suggested to play critical roles in the development of renal cysts. However, although several therapeutic targets for PKD have been suggested, no early diagnosis or effective treatments are currently available. Current developments are active for treatment of PKD including inhibitors or antagonists of PPAR-${\gamma}$, TNF-${\alpha}$, CDK and VEGF. These drugs are potential therapeutic targets in PKD, and need to be determined about pathological functions in human PKD. It has recently been reported that the alteration of epigenetic regulation, as well as gene mutations, may affect the pathogenesis of PKD. In this review, we will discuss recent approaches to PKD therapy. It provides important information regarding potential targets for PKD.

• Childhood Kidney Diseases
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• v.22 no.2
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• pp.64-66
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• 2018

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease and causes terminal chronic renal failure. ADPKD is characterized by bilateral multiple renal cysts, which are produced by mutations of the PKD1 and PKD2 genes. PKD1 is located on chromosome 16 and encodes a protein that is involved in cell cycle regulation and intracellular calcium transport in epithelial cells and is responsible for 85% of ADPKD cases. Although nine cases of unilateral ADPKD with contralateral kidney agenesis have been reported, there have been no reports of early childhood ADPKD. Here, we report the only case of unilateral ADPKD with contralateral kidney dysplasia in the world in a four year-old girl who was intrauterinely diagnosed since she was 20 weeks old and followed for four years until present.

• Journal of Genetic Medicine
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• v.13 no.1
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• pp.36-40
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• 2016

Tuberous sclerosis complex (TSC, MIM#191100) is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of TSC1 encoding hamartin or TSC2 encoding tuberin and characterized by seizure, mental retardation, and multiple hamartomas or benign tumors in the skin, brain, retina, heart, kidney, and lungs. The TSC2 gene on chromosome 16p13.3 lies adjacent to the PKD1 gene which is responsible for autosomal dominant polycystic kidney disease (MIM#173900). The TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1 CGDS, MIM#600273) is caused by deletion of both TSC2 and PKD1 gene. We recently experienced a 15 month-old boy and a 26 month-old girl with TSC2/PKD1 CGDS confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis. They showed not only typical neurologic manifestations of TSC such as epilepsy, subependymal nodules, and subcortical tubers, but also polycystic kidney disease. The contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with enlarged polycystic kidneys and TSC. MLPA analysis is a useful method for the genetic confirmation of TSC2/PKD1 CGDS.

• Genomics & Informatics
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• v.10 no.1
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• pp.16-22
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• 2012

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the $PKD1$ and $PKD2$ genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of $PKD1$ and $PKD2$ demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that $PKD1$ and $PKD2$ probably play important roles during normal renal tubular development. However, their precise role in development and the cellular mechanisms of cyst formation induced by $PKD1$ and $PKD2$ mutations are not fully understood. To address this question, we presently created $Pkd2$ knockout and $PKD2$ transgenic mouse embryo fibroblasts. We used a mouse oligonucleotide microarray to identify messenger RNAs whose expression was altered by the overexpression of the $PKD2$ or knockout of the $Pkd2$. The majority of identified mutations was involved in critical biological processes, such as metabolism, transcription, cell adhesion, cell cycle, and signal transduction. Herein, we confirmed differential expressions of several genes including aquaporin-1, according to different $PKD2$ expression levels in ADPKD mouse models, through microarray analysis. These data may be helpful in $PKD2$-related mechanisms of ADPKD pathogenesis.

• Animal cells and systems
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• v.10 no.2
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• pp.65-71
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• 2006

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited renal disorders in the world. Mutations in PKD1 located on chromosome 16p13.3 are responsible for 85% of all the ADPKD patients whereas mutations in PKD2 on chromosome 4q21-23 are responsible for the rest of the cases. Genetic heterogeneity and the problems of mutation detection in PKD1 suggest that linkage analysis is an important approach to study the genetics of ADPKD. To evaluate the availability of six (CA)n microsatellite markers for the linkage analysis of ADPKD in the Korean population, we examined the allele frequencies and heterozygosities of the markers. With the exception of KG8, five markers were highly informative, with PIC values over 0.5, but the PIC value of KG8 marker was less informative than other five markers because of the low number of alleles. Therefore, this study will be useful in linkage analysis for ADPKD families in the Korean population.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.51-54
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• 2020

Since the American College of Medical Genetics and Genomics and Association of Molecular Pathology published their guidelines in 2015, most interpretations of genetic tests have followed them. However, all variants have only limited evidence along 28 interpretation standards, especially de novo variants. When de novo variants, which are classified as variants of uncertain significance (VUS) due to lack of evidence, are detected, segregation in the affected family could provide an important key to clarifying the variants. Autosomal dominant polycystic kidney disease is the most common inherited kidney disorder with pathogenic variants in the PKD1 or PKD2 genes. We detected a novel in-frame deletion variant in the PKD1 gene, c.7575_7577del (p.(Cys2526del)), which was interpreted as a VUS. We analyzed this variant in a Korean family to decide for segregation. Here, we report the variant as a likely pathogenic variant based on the evidence of segregation in three affected relatives and two unaffected members.

• Journal of Veterinary Clinics
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• v.31 no.5
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• pp.466-468
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• 2014

Polycystic kidney disease (PKD) is characterized by multiple cysts within the renal parenchyma and is a common heritable disease in humans, dogs, and cats. However, a few cases of PKD have been described in captive pygmy hippopotamuses. Bilateral PKD was observed in a 33-year-old, 198-kg female pygmy hippopotamus during its necropsy in Seoul Zoo on 15 January 2013. The diagnosis of PKD was confirmed by gross findings and histopathological examination. One kidney was slightly enlarged, and the lower portion of other kidney contained a large cyst filled with light yellow, watery fluid. Both kidneys had numerous, variably sized fluid-filled cysts of 2 to 20 mm in diameter. Considerable portions of the renal cortex and medulla were replaced by cysts. Microscopic inspection showed that the cysts were lined with low cuboidal to flat epithelial cells. The present case report of PKD in a pygmy hippopotamus is the first in Korea.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.277-286
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• 2020

Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

• The Journal of Internal Korean Medicine
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• v.42 no.3
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• pp.225-238
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• 2021

Objective: This research reviews and investigates the trends in recent clinical studies of polycystic kidney disease (PKD) in China. Method: We searched for clinical studies discussing Oriental medicine-based treatments for PKD in the China National Knowledge Infrastructure (CNKI) database. Thirteen clinical articles published from 2001 to 2019 were analyzed. The search focused on the authors, publication year, type of study, purposes of study, method and duration of treatment, evaluation criteria, and results of the selected articles. Results: Of the articles from the database, 9 case series and 4 randomized controlled trials (RCTs) were analyzed. Ten articles used herbal medicine; 4 used herbal medicine for external use. Gamigyejibokryeong-hwan was the most common herbal prescription. The most frequently used herb was Polia Sclerotium (茯苓), and Cnidii Rhizoma (川芎) was employed in all the external uses. All 13 studies confirmed the efficacy of Oriental medicine treatments. Conclusion: 1. Scientifically designed and more varied clinical studies are required to develop treatments for PKD. 2. The current study could be used as basic data in future clinical studies on treatment and further studies of PKD.