P2X&lt;sub&gt;7&lt;/sub&gt; Receptors Are Expressed during Mouse Nephrogenesis and in Collecting Duct Cysts of the &lt;i&gt;cpk/cpk&lt;/i&gt; Mouse

Hillman, Katherine A.; Johnson, Tanya M.; Winyard, Paul J D; Burnstock, Geoffrey; Unwin, Robert J.; Woolf, Adrian S.

doi:10.1159/000049896

Cited by 31 publications

(32 citation statements)

References 28 publications

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“…Previous reports have shown that, in healthy mice, P2X7 is expressed in the renal collecting duct but not in the glomeruli or other tubules [62]. The function of P2X7 in collecting duct remains poorly understood.…”

Section: Discussionmentioning

confidence: 95%

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Beaucage

Xiao

Pollmann

et al. 2013

Purinergic Signalling

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The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9-12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9-and 12-month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age-and sex-dependent manner.

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Section: Discussionmentioning

confidence: 95%

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Beaucage

Xiao

Pollmann

et al. 2013

Purinergic Signalling

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“…This is not surprising given their past tutelage in the Burnstock group. They have led the field in determining that P2X 7 expression emerges in apoptotic and/ or diseased renal epithelial, interstitial, and glomerular cells, which is well documented by several groups [86,96,[98][99][100]. In particular, emergence of abundant P2X 7 expression has been documented in mouse models and in human cells and tissues within autosomal recessive (ARPKD) and autosomal dominant (ADPKD) polycystic kidney disease [96,[98][99][100].…”

Section: Nucleotide and Nucleoside Receptor Expression Along The Nephronmentioning

confidence: 99%

“…They have led the field in determining that P2X 7 expression emerges in apoptotic and/ or diseased renal epithelial, interstitial, and glomerular cells, which is well documented by several groups [86,96,[98][99][100]. In particular, emergence of abundant P2X 7 expression has been documented in mouse models and in human cells and tissues within autosomal recessive (ARPKD) and autosomal dominant (ADPKD) polycystic kidney disease [96,[98][99][100]. In diabetic and hypertensive rats, P2X 7 expression emerged and was abundant in multiple vascular and nonvascular cell types of the glomerulus [96,[98][99][100].…”

Section: Nucleotide and Nucleoside Receptor Expression Along The Nephronmentioning

confidence: 99%

“…In particular, emergence of abundant P2X 7 expression has been documented in mouse models and in human cells and tissues within autosomal recessive (ARPKD) and autosomal dominant (ADPKD) polycystic kidney disease [96,[98][99][100]. In diabetic and hypertensive rats, P2X 7 expression emerged and was abundant in multiple vascular and nonvascular cell types of the glomerulus [96,[98][99][100]. It is important to note that activation of the P2X 7 receptor channel also evokes the appearance of the opening of large pores that allow dyes to enter cells and that are used to detect apoptotic cells.…”

Section: Nucleotide and Nucleoside Receptor Expression Along The Nephronmentioning

confidence: 99%

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Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Hovater

Olteanu

Welty

et al. 2008

Purinergic Signalling

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The nephron is the functional unit of the kidney. Blood and plasma are continually filtered within the glomeruli that begin each nephron. Adenosine 5′ triphosphate (ATP) and its metabolites are freely filtered by each glomerulus and enter the lumen of each nephron beginning at the proximal convoluted tubule (PCT). Flow rate, osmolality, and other mechanical or chemical stimuli for ATP secretion are present in each nephron segment. These ATP-release stimuli are also different in each nephron segment due to water or salt permeability or impermeability along different luminal membranes of the cells that line each nephron segment. Each of the above stimuli can trigger additional ATP release into the lumen of a nephron segment. Each nephron-lining epithelial cell is a potential source of secreted ATP. Together with filtered ATP and its metabolites derived from the glomerulus, secreted ATP and adenosine derived from cells along the nephron are likely the principal two of several nucleotide and nucleoside candidates for renal autocrine and paracrine ligands within the tubular fluid of the nephron. This minireview discusses the first principles of purinergic signaling as they relate to the nephron and the urinary bladder. The review discusses how the lumen of a renal tubule presents an ideal purinergic signaling microenvironment. The review also illustrates how remodeled and encapsulated cysts in autosomal dominant polycystic kidney disease (ADPKD) and remodeled pseudocysts in autosomal recessive PKD (ARPKD) of the renal collecting duct likely create an even more ideal microenvironment for purinergic signaling. Once trapped in these closed microenvironments, purinergic signaling becomes chronic and likely plays a significant epigenetic and detrimental role in the secondary progression of PKD, once the remodeling of the renal tissue has begun. In PKD cystic microenvironments, we argue that normal purinergic signaling within the lumen of the nephron provides detrimental acceleration of ADPKD once remodeling is complete.

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“…It was reported that purinergic signaling plays an important role in cystogenesis during both ADPKD and ARPKD 31,32 . Cyst cells of PCK rats have previously been shown to exhibit low basal [Ca 2+ ] i and loss of flow-mediated [Ca 2+ ] i signaling compared to healthy non-dilated collecting ducts of SD rats 13 .…”

Section: Representative Resultsmentioning

confidence: 99%

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Pavlov

Ilatovskaya

Palygin

et al. 2015

JoVE

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Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca 2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca 2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. Video LinkThe video component of this article can be found at

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P2X<sub>7</sub> Receptors Are Expressed during Mouse Nephrogenesis and in Collecting Duct Cysts of the <i>cpk/cpk</i> Mouse

Cited by 31 publications

References 28 publications

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

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