Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD.

Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD. Am J Physiol Renal Physiol. 2019 Oct 21;: Authors: Arkhipov SN, Potter DL, Geurts AM, Pavlov TS Abstract The severity of polycystic kidney diseases depends on the counterbalancing of genetic predisposition and environmental factors exerting permissive or protective influence on cyst development. One poorly characterized phenomenon in the cystic epithelium is abnormal purinergic signaling. Earlier experimental studies revealed high importance of the ionotropic P2X receptors (particularly, P2X7) in the pathophysiology of the cyst wall. To study mechanisms of P2X7 involvement in cyst growth and the aspects of targeting these receptors in PKD treatment we performed a CRISPR/SpCas9-mediated global knockout of the P2rx7 gene in PCK rats, a model of autosomal recessive PKD (ARPKD). A single base insertion in exon 2 of the P2rx7 gene leads to lack of P2X7 protein in the renal tissues of homozygous mutant animals that did not affect their viability or renal excretory function. However, PCK.P2rx7-/- rats demonstrated slower cyst growth (but not formation of new cysts) in comparison to heterozygous and PCK.P2rx7+/+ littermates. P2X7 receptors are known to activate pannexin-1, a plasma channel capable of releasing ATP, and we here found that pannexin-1 expression in cystic epithelium is significantly higher than in non-dilated tubules. P2X7 deficiency reduces renal pannexin-1 prote...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Autosomal-dominant polycystic kidney disease (ADPKD) induces a secretory phenotype, resulting in multiple fluid-filled cysts. We have previously demonstrated that VX-809, a corrector of the cystic fibrosis transmembrane conductance regulator (CFTR), reduces cyst growth. Here, we show that in normal mice CFTR is located within the cells and also at the apical and basolateral membranes. However, in polycystic kidney disease (pkd1)-knockout mice, CFTR was located at the plasma membrane, consistent with its role in cAMP-dependent fluid secretion. In cystic mice, VX-809 treatment increased CFTR levels at the apical membrane and...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
Publication date: Available online 5 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Juan Lorenzo Pablo, Anna GrekaIon channels are critical to kidney function, and their dysregulation leads to several distinct kidney diseases. Of the diversity of ion channels in kidney cells, the transient receptor potential (TRP) superfamily of proteins plays important and varied roles in both maintaining homeostasis as well as in causing disease. Recent work showed that TRPC5 blockers could successfully protect critical components of the kidney filter both in vitro and in vivo, thus revealing TRPC5 as a tract...
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
We report a child with bilateral enlarged, echogenic, polycystic kidneys with end-stage renal disease, anemia and metabolic acidosis caused by biallelic novel pathogenic variants, c.796+5G>A and c.1789C>T in INVS. We show that the variant, c.796+5G>A disrupts the canonical splicing and nonsense variant, c.1789C>T results in nonsense mediated decay. PMID: 31706999 [PubMed - as supplied by publisher]
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
CONCLUSION: FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment. PMID: 31694015 [PubMed - as supplied by publisher]
Source: American Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: Am J Nephrol Source Type: research
Condition:   Polycystic Kidney Disease, Adult Intervention:   Drug: Lixivaptan Sponsor:   Palladio Biosciences Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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
Abstract Studies in rodents with reduced nephron mass suggest a strong positive correlation between dietary phosphate consumption and CKD progression. Prior work by our group demonstrated dietary phosphate restriction can prevent tubular injury and microcyst formation in rodents with glomerulonephritis. Tubular injury and cystic dilation of tubules are key contributors to kidney function decline in polycystic kidney disease (PKD). Here, we determined if dietary phosphate restriction slows renal cyst growth and fibrosis in a mouse model of PKD. Pcy/pcy mice received a normal phosphate (0.54%) or a phosphate-restric...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
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
Authors: Belengeanu V, Marian D, Hosszu T, Ogodescu AS, Belengeanu AD, Samoilă C, Freiman P, Lile IE Abstract Orofaciodigital syndrome (OFDS) is a collective term for a rare inherited disorder that displays a wide phenotypic and genetic heterogeneity. The findings of diagnostic are the combination of the characteristic oral, facial and digital anomalies. In this heterogeneous group, the diagnosis of OFDI focuses on the association of the oro-dental, digital and cerebral malformations, polycystic kidney disease and several other manifestations. In this article, we report and discuss the case of a girl with OFDI syn...
Source: Romanian Journal of Morphology and Embryology - Category: General Medicine Tags: Rom J Morphol Embryol Source Type: research
Authors: Mateescu DŞ, Gheonea M, Bălgrădean M, Enculescu AC, Şerbănescu MS, Nechita F, Pirici D, Rogoveanu I Abstract A significant cause of end-stage renal disease in infants (40% to 50% of cases) is represented by the group of renal cystic diseases. Actually, the fourth cause of renal failure in young adults is the autosomal dominant polycystic kidney disease (ADPKD). Moreover, the most common genetically inherited kidney disease was proved to be ADPKD, affecting 1-5 per 10 000 individuals. The study was conducted over a period of three years (July 26, 2015-October 30, 2018) on 22 patients aged between two d...
Source: Romanian Journal of Morphology and Embryology - Category: General Medicine Tags: Rom J Morphol Embryol Source Type: research
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