Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury
In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine an...
Source: AJP: Renal Physiology - March 8, 2017 Category: Urology & Nephrology Authors: Shi, Y., Xu, L., Tang, J., Fang, L., Ma, S., Ma, X., Nie, J., Pi, X., Qiu, A., Zhuang, S., Liu, N. Tags: RESEARCH ARTICLE Source Type: research
Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms
Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA). An involvement of major hormones like angi...
Source: AJP: Renal Physiology - March 1, 2017 Category: Urology & Nephrology Authors: Blankenstein, K. I., Borschewski, A., Labes, R., Paliege, A., Boldt, C., McCormick, J. A., Ellison, D. H., Bader, M., Bachmann, S., Mutig, K. Tags: RESEARCH ARTICLE Source Type: research
Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats
The role of cannabinoid type 1 (CB1) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical infusion of 0.5% acetic acid (AA) was determined in α-chloralose anesthetized cats. AA irritation significantly (P < 0.01) reduced bladder capacity to 36.6 ± 4.8% of saline control capacity. Tibial nerve stimulation (TNS) at two or four times threshold (2T or 4T) intensity for inducing toe movement inhibited bladder overactivity and significantly (P < 0.01) increased bladder capacity to 69.2 ± 9.7 and 79.5 ± 7.2% of saline control, respectively. AM 251 (a CB1...
Source: AJP: Renal Physiology - March 1, 2017 Category: Urology & Nephrology Authors: Jiang, X., Yu, M., Uy, J., Fuller, T. W., Jones, C., Shen, B., Wang, J., Roppolo, J. R., de Groat, W. C., Tai, C. Tags: RESEARCH ARTICLE Source Type: research
Phosphodiesterase 5 inhibition ameliorates angiotensin II-dependent hypertension and renal vascular dysfunction
Changes in renal hemodynamics have a major impact on blood pressure (BP). Angiotensin (Ang) II has been shown to induce vascular dysfunction by interacting with phosphodiesterase (PDE)1 and PDE5. The predominant PDE isoform responsible for renal vascular dysfunction in hypertension is unknown. Here, we measured the effects of PDE5 (sildenafil) or PDE1 (vinpocetine) inhibition on renal blood flow (RBF), BP, and renal vascular function in normotensive and hypertensive mice. During acute short-term Ang II infusion, sildenafil decreased BP and increased RBF in C57BL/6 (WT) mice. In contrast, vinpocetine showed no effect on RBF...
Source: AJP: Renal Physiology - March 1, 2017 Category: Urology & Nephrology Authors: Thieme, M., Sivritas, S. H., Mergia, E., Potthoff, S. A., Yang, G., Hering, L., Grave, K., Hoch, H., Rump, L. C., Stegbauer, J. Tags: RESEARCH ARTICLE Source Type: research
In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury?
Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized 13C-pyruvate MRI enables noninvasive accurate quantification of th...
Source: AJP: Renal Physiology - March 1, 2017 Category: Urology & Nephrology Authors: Nielsen, P. M., Laustsen, C., Bertelsen, L. B., Qi, H., Mikkelsen, E., Kristensen, M. L. V., Norregaard, R., Stodkilde-Jorgensen, H. Tags: RESEARCH ARTICLE Source Type: research
The hypoxanthine-xanthine oxidase axis is not involved in the initial phase of clinical transplantation-related ischemia-reperfusion injury
The hypoxanthine-xanthine oxidase (XO) axis is considered to be a key driver of transplantation-related ischemia-reperfusion (I/R) injury. Whereas interference with this axis effectively quenches I/R injury in preclinical models, there is limited efficacy of XO inhibitors in clinical trials. In this context, we considered clinical evaluation of a role for the hypoxanthine-XO axis in human I/R to be relevant. Patients undergoing renal allograft transplantation were included (n = 40) and classified based on duration of ischemia (short, intermediate, and prolonged). Purine metabolites excreted by the reperfused kidney (arteri...
Source: AJP: Renal Physiology - March 1, 2017 Category: Urology & Nephrology Authors: Wijermars, L. G. M., Bakker, J. A., de Vries, D. K., van Noorden, C. J. F., Bierau, J., Kostidis, S., Mayboroda, O. A., Tsikas, D., Schaapherder, A. F., Lindeman, J. H. N. Tags: RESEARCH ARTICLE Source Type: research
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(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Tags: CORRIGENDA Source Type: research
Renin-angiotensin system transgenic mouse model recapitulates pathophysiology similar to human preeclampsia with renal injury that may be mediated through VEGF
Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred: female hAGT x male hREN for preeclampsia (PRE) model and female WT x male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheliosis ...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Denney, J. M., Bird, C., Gendron-Fitzpatrick, A., Sampene, E., Bird, I. M., Shah, D. M. Tags: RESEARCH ARTICLE Source Type: research
Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells
Previous studies have shown that increased parathyroid hormone (PTH) attributable to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unknown, endothelial cells (ECs) have recently been demonstrated to participate in calcification in part by providing chondrogenic cells via the endothelial-to-mesenchymal transition (EndMT). Therefore, this study aimed to investigate whether elevated PTH could induce endothelial-to-chondrogenic transition in aortic ECs and to determine the possible underlying signaling pathw...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Wu, M., Zhang, J.-D., Tang, R.-N., Crowley, S. D., Liu, H., Lv, L.-L., Ma, K.-L., Liu, B.-C. Tags: RESEARCH ARTICLE Source Type: research
Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney
This study’s purpose was to determine NaDC1's expression in normal and neoplastic human kidneys. Immunoblot analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61 kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule of normal human kidney tissue; well-preserved proximal tubule brush border was clearly labeled. Apical NaDC1 expression was evident throughout the entire proximal tubule, including the initial proximal convoluted tubule, as identified by origination from the glomerular tuft, and extending through the terminal of the proximal tubule, the proximal straigh...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Lee, H.-W., Handlogten, M. E., Osis, G., Clapp, W. L., Wakefield, D. N., Verlander, J. W., Weiner, I. D. Tags: RESEARCH ARTICLE Source Type: research
Effects of exogenous desmopressin on a model of heat stress nephropathy in mice
Recurrent heat stress and dehydration have recently been shown experimentally to cause chronic kidney disease (CKD). One potential mediator may be vasopressin, acting via the type 2 vasopressin receptor (V2 receptor). We tested the hypothesis that desmopressin accelerates CKD in mice subjected to heat stress and recurrent dehydration. Recurrent exposure to heat with limited water availability was performed in male mice over a 5-wk period, with one group receiving desmopressin two times daily and the other group receiving vehicle. Two additional control groups were not exposed to heat or dehydration and received vehicle or ...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Roncal-Jimenez, C. A., Milagres, T., Andres-Hernando, A., Kuwabara, M., Jensen, T., Song, Z., Bjornstad, P., Garcia, G. E., Sato, Y., Sanchez-Lozada, L. G., Lanaspa, M. A., Johnson, R. J. Tags: RESEARCH ARTICLE Source Type: research
Prorenin receptor controls renal branching morphogenesis via Wnt/{beta}-catenin signaling
The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Renal branching morphogenesis, defined as growth and branching of the ureteric bud (UB), is essential for mammalian kidney development. Previously, we demonstrated that conditional ablation of the PRR in the UB in PRRUB–/– mice causes severe defects in UB branching, resulting in marked kidney hypoplasia at birth. Here, we investigated the UB transcriptome using whole genome-based analysis of gene expression in UB cells, FACS-isolated from PRRUB–/–, and control kidneys at ...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Song, R., Janssen, A., Li, Y., El-Dahr, S., Yosypiv, I. V. Tags: RESEARCH ARTICLE Source Type: research
Cilostazol inhibits uremic toxin-induced vascular smooth muscle cell dysfunction: role of Axl signaling
This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling. We investigated the effect of P-cresol and cilostazol on Axl signaling in A7r5 rat VSMCs and the rat and human CKD models. From the in vivo CKD rats and patients, aortic tissue exhibited significantly decreased Axl expression after cilostazol treatment. P-cresol increased Axl, proliferating of cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and matrix metalloproteinase-2 (MMP-2) expressions, decreased caspase-3 expression, and was accompanied by i...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Lee, C.-H., Hung, Y.-J., Shieh, Y.-S., Chien, C.-Y., Hsu, Y.-J., Lin, C.-Y., Chiang, C.-F., Huang, C.-L., Hsieh, C.-H. Tags: RESEARCH ARTICLE Source Type: research
IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats
T cells have been implicated in the pathogenesis of acute kidney injury (AKI) and its progression to chronic kidney disease (CKD). Previous studies suggest that Th17 cells participate during the AKI-to-CKD transition, and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell-deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal ischemis-reperfusion (I/R) was performed on T cell-deficient athymic rats (Foxn1rnu–/rnu–) and control euthymic rats (Foxn1rnu–...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Mehrotra, P., Collett, J. A., McKinney, S. D., Stevens, J., Ivancic, C. M., Basile, D. P. Tags: RESEARCH ARTICLE Source Type: research
A perspective on chronic kidney disease progression
Chronic kidney disease (CKD) will progress to end stage without treatment, but the decline of renal function may not be linear. Compared with glomerular filtration rate and proteinuria, new surrogate markers, such as kidney injury molecule-1, neutrophil gelatinase-associated protein, apolipoprotein A-IV, and soluble urokinase receptor, may allow potential intervention and treatment in the earlier stages of CKD, which could be useful for clinical trials. New omic-based technologies reveal potential new genomic and epigenomic mechanisms that appear different from those causing the initial disease. Various clinical studies al...
Source: AJP: Renal Physiology - February 28, 2017 Category: Urology & Nephrology Authors: Zhong, J., Yang, H.-C., Fogo, A. B. Tags: REVIEW Source Type: research
