The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP₃R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP₃R3. The effect of IP₃R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP₃R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP₃R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP₃R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP₃R3, which was accompanied by a subcellular redistribution process in which IP₃R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP₃R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP₃R3 are involved in promoting renal cyst development, which implies IP₃R3 as a potential therapeutic target of ADPKD.
Animals ; Dogs ; Mice ; Cysts/genetics* ; Inositol 1,4,5-Trisphosphate Receptors/pharmacology* ; Kidney/metabolism* ; Polycystic Kidney Diseases/metabolism* ; Polycystic Kidney, Autosomal Dominant/drug therapy* ; Madin Darby Canine Kidney Cells

TRPP subfamily is an important member of transient receptor potential family. It has six transmembrane (TM) domains, a large extracellular loop between the first and second TM and 2-4 ankyrin repeats in the N terminal. TRPP subfamily includes TRPP2, TRPP3, TRPP5 etc. There are several differences in their structure, activation mode and function. TRPP subfamily is involved in many physiological mechanisms and its abnormal structure can lead to the formation of polycystic kidney. This subfamily is also closely related to gustation. In this review, we summarize recent research findings of TRPP subfamily and its association with polycystic kidney diseases.
Humans ; Polycystic Kidney Diseases ; genetics ; metabolism ; TRPP Cation Channels ; chemistry ; genetics ; physiology

Primary gout is an as yet undefined inborn error of metabolism characterized by hyperuricemia, recurrent attacks of acute arthritis ordinarily responsive to colchicine, and in many instances eventually by tophaus deposit of urate. Also secondary gouty symptom complexes can be induced by various causes. The kidney is involved about 15 ~ 20% of gout and represented clinically as albuminuria, which may persist for several decades before nitrogen retention ensues, and progressively reveal the impairment of concentrating ability and delayed excretion of PSP. This patient has been chronically suffered from the right flank pain and intermittent oliguria due to bilateral ureteral obstruction by uric acid stone and crystals for five years and exploratory operation for stone turned out as gouty kidney complicated in the polycystic kidney. The authors report this case with review of the literature.
Albuminuria ; Arthritis ; Colchicine ; Flank Pain ; Gout ; Humans ; Hyperuricemia ; Kidney* ; Metabolism ; Nitrogen ; Oliguria ; Polycystic Kidney Diseases ; Ureteral Obstruction ; Uric Acid

To study the expression of beta-human chorionic gonadotropin (beta hCG) genes in renal cell carcinomas (RCC) and benign renal disease tissues, nested reverse transcription-polymerase chain reaction (RT-PCR) and restriction endonuclease analysis were employed to detect the expression of beta hCG genes in 44 cases of RCC tissues and 24 cases of benign renal disease tissues. It was found that 52% RCC samples revealed positive for beta hCG mRNA expression. Positive rate in advanced stage and poorly differentiated RCC was higher, but there was no significant difference. The positive rate of beta hCG mRNA expression was 54% in 24 cases of benign renal tissues, including 3 cases out of 6 polycystic kidneys, 7 cases out of 13 renal atrophies, 2 cases out of 2 oncocytomas and 1 case out of 2 pyonephrotic kidneys. beta 7 was most frequently transcribed subtype gene independent on the histology. These findings suggested beta hCG gene transcription is not only involved in RCC but also in benign renal diseases.
Adult ; Biomarkers, Tumor ; Carcinoma, Renal Cell ; genetics ; metabolism ; Chorionic Gonadotropin, beta Subunit, Human ; biosynthesis ; genetics ; Humans ; Kidney ; metabolism ; Kidney Diseases ; genetics ; metabolism ; Kidney Neoplasms ; genetics ; metabolism ; Polycystic Kidney Diseases ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

One of the most widespread cellular organelles in nature is cilium, which is found in many unicellular and multicellular organisms. Formerly thought to be a mostly vestigial organelle, the cilium has been discovered in the past several decades to play critical motile and sensory roles involved in normal organogenesis during development. The role of cilia has also been implicated in an ever increasing array of seemingly unrelated human diseases, including blindness, kidney cysts, neural tube defects and obesity. In this article we review some of the recent developments in research on cilia, and how defects in ciliogenesis and function can give rise to developmental disorders and disease.
Abnormalities, Multiple ; pathology ; Animals ; Cerebellar Diseases ; genetics ; pathology ; Cilia ; physiology ; ultrastructure ; Flagella ; physiology ; Hedgehog Proteins ; metabolism ; Humans ; Models, Animal ; Polycystic Kidney Diseases ; pathology ; Protein Transport ; Signal Transduction ; Wnt Proteins ; metabolism

The term congenital anomalies here refers to structural defect (congenital malformations, deformations, disruptions and dysplasias), chromosomal abnormalities, inborn errors of metabolism and hereditary disease. The prevalence of major congenital malformation (i.e., defects either incompatible with life or severe enough to interfere with normal living) is about 2% to 3%. In the past, infection was one of the major cause of perinatal morbidity and mortality, but owing to the development of antibiotics and intensive care, congenital anomalies are becoming a major cause of perinatal morbidity and mortality. Perinatal diagnosis of congenital anomalies is becoming more important because appropriate perinatal care may minimize the effect of congenital anomalies. This report was based on the 234 cases of the congenital anomalies among 8,099 newborns delivered at Dankook University Hospital from Mar. 1st, 1995 to Feb. 28th, 2000. The analyzed results were as follows: 1. The overall incidence of the congenital anomalies was 2.9%. The incidence of congenital anomalies in male newborns (141, 60.2%) was statistically significantly higher than that of female (90, 38.5%) and ambiguous (3, 1.3%). 2. The incidence of the congenital anomalies of 21-25 year old maternal age was the lowest among each other age group. The incidence of this group was 1.6%, of less than 20 year old group was 2.7%, of over 35 year old group was 2.9%. But there was no statistically significant difference among each maternal age groups. 3. There was no statistically significant difference in the incidences of congenital anomalies between parity. 4. The incidence of low-birth weight less than 2,500 g in congenital anomalies was 9.2%, which was 5.1 times higher than that of the more than 2,500 g. 5. The incidence of vertex presentation in congenital anomalies (192, 82.1%) was very high compared to breech presentation (42, 17.9%). 6. In the method of deliveries, vaginal deliveries was 131 cases (56.0%) and cesarean section was 103 cases (44.0%). 7. The incidence of the congenital anomalies in stillbirth was 28.4%, which was 13 times higher than that of the live birth. 8. The perinatal mortality rate in congenital anomalies were 93 cases (39.7%) and stillbirths were 62 cases (28.4%). 9. When classified according to the type of congenital anomalies, the rate of the incidence was 13.3% (31 cases) in central nervous system, 9.4% (22 cases) in neck and face anomaly, 6.8% (16 cases) in cardiac anomaly, 1.3% (3 cases)in pulmonary anomaly, 5.5% (13 cases) in gastrointestinal anomaly, 13.7% (32 cases) in genitourinary anomaly, 18.4% (43 cases) in musculoskeletal anomaly, 9.0% (21 cases) in skin and soft tissue anomaly, 14.1% (33 cases) in multiple anomaly and 5.5% (13 cases) in chromosomal anomaly. The most common major congenital anomalies was hydrocephalus (14 cases, 5.9%) and polycystic kidney (14 cases, 5.9%). The rate of perinatal mortality of the congenital anomalies was 38.5%, particularly it was the highest in the CNS anomalies which were 89.7%, the next 50.0% in cardiopulmonary anomalies.
Adult ; Anti-Bacterial Agents ; Breech Presentation ; Central Nervous System ; Cesarean Section ; Chromosome Aberrations ; Diagnosis ; Female ; Genetic Diseases, Inborn ; Humans ; Hydrocephalus ; Incidence ; Infant, Newborn ; Critical Care ; Live Birth ; Male ; Maternal Age ; Metabolism, Inborn Errors ; Mortality ; Neck ; Parity ; Perinatal Care ; Perinatal Mortality ; Polycystic Kidney Diseases ; Pregnancy ; Prevalence ; Skin ; Stillbirth ; Ultrasonography ; Young Adult

OBJECTIVETo analyze PKHD1 gene mutation in a family affected with autosomal recessive polycystic kidney disease (ARPKD).

METHODSGenomic DNA was extracted from peripheral and cord blood samples obtained from the parents and the fetus. Potential mutations were identified using targeted exome sequencing and confirmed by Sanger sequencing. Pathogenicity of the mutation was analyzed using PolyPhen-2 and SIFT software.

RESULTSCompound heterozygous mutations of c.11314C>T (p.Arg3772*) and a novel missense c.889T>A (p.Cys297Ser) of the PKHD1 gene were identified in the fetus. The mother was found to have carried the c.11314C>T mutation, while the father was found to have carried the c.889T>A mutation. PolyPhen-2 and SIFT predicted that the c.889T>A mutation is probably damaging.

CONCLUSIONA novel mutation in PKHD1 gene was detected in our ARPKD family. Compound heterozygous PKHD1 mutations were elucidated to be the molecular basis for the fetus affected with ARPKD, which has facilitated genetic counseling and implement of prenatal diagnosis for the family.

Abortion, Eugenic ; Adult ; Amino Acid Sequence ; Base Sequence ; DNA Mutational Analysis ; Family Health ; Fatal Outcome ; Female ; Fetal Diseases ; diagnostic imaging ; genetics ; Fetus ; abnormalities ; metabolism ; Humans ; Male ; Mutation ; Polycystic Kidney, Autosomal Recessive ; diagnostic imaging ; embryology ; genetics ; Pregnancy ; Receptors, Cell Surface ; genetics ; Sequence Homology, Amino Acid ; Ultrasonography, Prenatal ; methods