Publications by authors named "Janet Klein"

Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. The body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape is a process that prevents the continuous decrease in serum sodium concentration even under conditions of sustained high plasma vasopressin levels.

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We previously showed that the phosphatases PP1/PP2A and PP2B dephosphorylate the water channel, AQP2, suggesting their role in water reabsorption. In this study, we investigated whether protein phosphatase 2A (PP2A) and protein phosphatase 2B (PP2B or calcineurin), which are present in the inner medullary collecting duct (IMCD), are regulators of urea and water permeability. Inhibition of calcineurin by tacrolimus increased both basal and vasopressin-stimulated osmotic water permeability in perfused rat IMCDs.

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Background: Muscle wasting is a common complication of chronic kidney disease (CKD) that is associated with higher mortality. Although the mechanisms of myofibre loss in CKD has been widely studied, the contribution of muscle precursor cell (MPC) senescence remains poorly understood. Senescent MPCs no longer proliferate and can produce proinflammatory factors or cytokines.

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Few noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT ( = 18) or a sham treatment ( = 16).

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Microplastics, plastic particles <5 mm in size, are of global concern as human-caused pollutants in marine and fresh waters, and yet little is known of their distribution, behaviour and ecological impact in the intertidal environment of South Australia. This study confirms for the first time, the presence of microplastic in the South Australian intertidal ecosystem by quantifying the abundance of particles in intertidal water and in the keystone species, the blue mussel, Mytilus spp., an important fisheries species, at ten and six locations respectively, along the South Australian coastline.

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Background: Our previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis.

Method: C57/BL6 mice received Acu/LFES treatment on hindlimb for 30 min once.

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Nephrogenic diabetes insipidus (NDI) patients produce large amounts of dilute urine. NDI can be congenital, resulting from mutations in the type-2 vasopressin receptor (V2R), or acquired, resulting from medications such as lithium. There are no effective treatment options for NDI.

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Aim: We have reported earlier that a high salt intake triggered an aestivation-like natriuretic-ureotelic body water conservation response that lowered muscle mass and increased blood pressure. Here, we tested the hypothesis that a similar adaptive water conservation response occurs in experimental chronic renal failure.

Methods: In four subsequent experiments in Sprague Dawley rats, we used surgical 5/6 renal mass reduction (5/6 Nx) to induce chronic renal failure.

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Adrenomedullin (ADM) is a vasodilator that causes natriuresis and diuresis. However, the direct effect of ADM on osmotic water permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether ADM and its ADM receptor components (CRLR, RAMP2, and 3) are expressed in rat inner medulla (IM) and whether ADM regulates osmotic water permeability in isolated perfused rat IMCDs.

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14-3-3γ is a small protein regulating its target proteins through binding to phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca-activated K (BK) channels revealed a putative 14-3-3 binding site in the COOH-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney.

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Article Synopsis
  • Uremic cardiomyopathy, a complication of chronic kidney disease (CKD), involves issues like high blood pressure, heart enlargement, and fibrosis.
  • The study tested dimethylthiourea (DMTU) as a urea transporter inhibitor in mice, finding it reduced CKD-related hypertension and cardiac hypertrophy while also lowering cardiac fibrosis markers.
  • In UT-A1/A3 knockout mice, the inhibition of urea transport led to decreased levels of proteins linked to fibrosis and hypertension, along with improved heart function through a reduction in harmful mRNA levels for renin and angiotensin-converting enzyme.
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Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs.

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Article Synopsis
  • Renal fibrosis plays a significant role in worsening chronic kidney disease, and a low-protein diet might help slow this progression, although the exact mechanism is unclear.
  • The study investigated the effects of inhibiting specific urea transporters (UT-A1 and UT-A3) on renal fibrosis in mice with unilateral ureteral obstruction (UUO), comparing wild-type (WT) mice to knockout mice lacking these transporters.
  • Results showed that WT mice experienced increased fibrosis markers and collagen after UUO, while UT-A1/A3 knockout mice exhibited significantly reduced fibrosis, suggesting that targeting urea transporter activity might lessen renal fibrosis severity.
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Renal fibrosis leads to end-stage renal disease, but antifibrotic drugs are difficult to develop. Chronic kidney disease often results in muscle wasting, and thereby increases morbidity and mortality. In this work, adeno-associated virus (AAV)-mediated overexpressing miR-29a was hypothesized to counteract renal fibrosis and muscle wasting through muscle-kidney crosstalk in unilateral ureteral obstruction (UUO) mice.

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Kidney fibrosis occurs in almost every type of chronic kidney disease. We found that microRNA (miR)-26a was decreased in the kidney, muscle, and exosomes of unilateral ureteral obstruction (UUO) mice. We hypothesized that exogenous miR-26 could suppresses renal fibrosis and muscle wasting in obstructive kidney disease.

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The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown.

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Uremic cardiomyopathy and muscle atrophy are associated with insulin resistance and contribute to chronic kidney disease (CKD)-induced morbidity and mortality. We hypothesized that restoration of levels would enhance exosome-mediated microRNA transfer to improve muscle wasting and cardiomyopathy that occur in CKD. Using next generation sequencing and qPCR, we found that CKD mice had a decreased level of in heart and skeletal muscle.

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Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis.

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Mammalian glycerophosphodiesterases (GDEs) were recently shown to be involved in multiple cellular signaling pathways. This study showed that decreased GDE5 expression results in accumulation of intracellular glycerophosphocholine (GPC), showing that GDE5 is actively involved in GPC/choline metabolism in 3T3-L1 adipocytes. Using 3T3-L1 adipocytes, we further studied the biological significance of GPC/choline metabolism during adipocyte differentiation.

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Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [ C, N] urea dynamics and Na distribution before and 60 min after glucagon infusion in six female rats.

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Excessive iron increases the incidence of diabetes and worsens diabetic complications. Reciprocally, diabetes induces iron loading, partially attributable to elevated intestinal iron export according to a recent report. Herein, we show that iron uptake and the mRNA expression of iron importer divalent metal transporter 1 (DMT1) were significantly increased in the duodenum of streptozotocin-induced diabetic mice.

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Acupuncture with low-frequency electrical stimulation (Acu/LFES) can prevent muscle atrophy by increasing muscle protein anabolism in mouse models of chronic kidney disease. During the treatment of muscle wasting, we found that Acu/LFES on the gastrocnemius muscle of the leg enhances renal blood flow. We also found that Acu/LFES increases exosome abundance and alters exosome-associated microRNA expression in the circulation.

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is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between and BP. In this study, we explored the effect of intercalated cell (IC) gene ablation on IC transporter abundance and function and on BP.

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Background: The treatment of muscle wasting is accompanied by benefits in other organs, possibly resulting from muscle-organ crosstalk. However, how the muscle communicates with these organs is less understood. Two microRNAs (miRs), miR-23a and miR-27a, are located together in a gene cluster and regulate proteins that are involved in the atrophy process.

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Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit.

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