GSE141355 Identification of ADPKD-related Genes and Pathways in the Cells Overexpressing PKD2

Contributors : Jin He ; Zhe ZhangSeries Type : Expression profiling by high throughput sequencingOrganism : Sus scrofaBased on the dosage effect hypothesis, renal cysts could arise in transgenic murine models overexpressing either PKD1 or PKD2, which are causal genes responsible for autosomal dominant polycystic kidney disease (ADPKD). To prove whether PKD genes overexpression is a universal mechanism driving cystogenesis or is merely restricted to rodents, other animal models are required. Previously, we failed to observe any renal cysts in a PKD2 overexpression transgenic pig model partially due to epigenetic silencing of transgene. Thus, to explore the feasibility of pig models and identification potential affected genes/pathways related to ADPKD, LLC-PK1 cells with high PKD2 expression were generated. RNA-seq was performed and MYC, IER3, ADM were found to be commonly upregulated genes in different PKD2 overexpression cell models. MYC is a well-characterized factor contributing to cystogenesis, and ADM is a biomarker for chronic kidney disease. Thus, theses genes might be indicators of disease progression. Additionally, some ADPKD associated pathways, e.g., MAPK, were also enriched in the cells. Besides, GO analysis demonstrated proliferation, apoptosis, cell cycle regulation, which are hall marks of ADPKD were disturbed. Therefore, our experiment not only identified some biomarkers or indictors regarding ADPKD, but also demonstrated high PKD2 expression would like to driv...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Sus scrofa Source Type: research

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Pan He Consistent with the gene dosage effect hypothesis, renal cysts can arise in transgenic murine models overexpressing either PKD1 or PKD2, which are causal genes for autosomal dominant polycystic kidney disease (ADPKD). To determine whether PKD gene overexpression is a universal mechanism driving cystogenesis or is merely restricted to rodents, other animal models are required. Previously, we failed to observe any renal cysts in a transgenic porcine model of PKD2 overexpression partially due to epigenetic silencing of the transgene. Thus, to explore the feasibility of porcine models and identify potential ge...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
Emerging evidence has demonstrated that epigenetic regulation plays a vital role in gene expression under normal and pathological conditions. Alterations in the expression and activation of histone methyltransferases (HMTs) have been reported in preclinical models of multiple kidney diseases, including acute kidney injury, chronic kidney disease, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma. Pharmacological inhibition of these enzymes has shown promise in preclinical models of those renal diseases. In this review, we summarize recent knowledge regarding expression and activation of various HMTs...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: Tolvaptan have a beneficial effect on ADPKD, but associated with an increase of adverse events on high dose when comparing with the placebo. Further RCTs studies on tolvaptan may be required to support this conclusion. PMID: 31793415 [PubMed - as supplied by publisher]
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research
Purpose of review Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor which regulates a wider range of downstream pathways than previously thought. This review focuses on the novel findings about the internal regulatory mechanisms of Nrf2, the expanding understanding of its role in maintaining cellular homeostasis and the attempts to broaden the clinical application of its activators. Recent findings Nrf2 is in charge of the maintenance of cellular homeostasis under stress and there exist the internal regulatory mechanisms for Nrf2 which have recently been elucidated. New downstream pathways o...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Mark Cooper and Merlin Thomas Source Type: research
2017 ended as a banner year for my family, but things didn’t look great at the start. A death sentence met us in a boxing ring, and we had to school ourselves on fighting to live. I never thought much about the 37 million American adults who suffer from kidney disease until my husband Neil became one of them. Celebrating our first year of marriage in 2001, we learned by accident through an unrelated medical exam that my husband has polycystic kidney disease, an illness which causes the kidneys to fill with cysts over time, rendering the organs unable to function properly. There is no cure. There was nothing to do but...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized health Healthcare medicine public health Source Type: news
We report a case of a 27-day-old male neonate admitted in our clinic for fever, foul-smelling urine, and diarrhea. A previous abdominal ultrasound at the age of 2 weeks revealed enlarged, hyperechoic kidneys, no abnormalities of the urinary exam. Clinical examination revealed poor general status, ill-looking face, diminished cutaneous turgor, distended abdomen, and palpable kidneys. Laboratory tests pointed out leukopenia, anemia, border-line platelet count, elevated inflammatory biomarker level, hyponatremia, hypoalbuminemia, proteinuria, leukocyturia, and hematuria. Both urine and blood cultures were positive for E. coli...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
CONCLUSIONS: This study suggests an important link between hypertension in pregnancy and ESKD. The patients were significantly younger, presented later and were more likely to have hypertensive nephropathy. Methamphetamine abuse appears to be a risk factor. The study suggests that all women with hypertensive disorders during pregnancy need further evaluation and follow-up postpartum. PMID: 31635591 [PubMed - in process]
Source: South African Medical Journal - Category: African Health Tags: S Afr Med J Source Type: research
Abstract Autophagy is a cellular homeostatic program for the turnover of cellular organelles and proteins, in which double-membraned vesicles (autophagosomes) sequester cytoplasmic cargos, which are subsequently delivered to the lysosome for degradation. Emerging evidence implicates autophagy as an important modulator of human disease. Macroautophagy and selective autophagy (e.g., mitophagy, aggrephagy) can influence cellular processes, including cell death, inflammation, and immune responses, and thereby exert both adaptive and maladaptive roles in disease pathogenesis. Autophagy has been implicated in acute kidn...
Source: Annual Review of Physiology - Category: Physiology Authors: Tags: Annu Rev Physiol Source Type: research
CONCLUSION: Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD. PMID: 31600749 [PubMed - as supplied by publisher]
Source: American Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: Am J Nephrol Source Type: research
In conclusion, our study suggests that a large percentage did not have nephrology care before initiating dialysis. The ones who were seen by nephrology before dialysis were significantly more likely to initiate dialysis using an AVF. A national focus on improving nephrology referral in advanced CKD may allow better utilization of AVF as the method of access at dialysis initiation. PMID: 31696849 [PubMed - in process]
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
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