Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation
In conclusion, proteins involved in transcellular Ca2+ and Mg2+ transport pathways increase during lactation, while expression of paracellular transport proteins remained unchanged. Increased fractional Ca2+ excretion can be explained by vitamin D-dependent intestinal hyperabsorption and bone demineralization, despite enhanced transcellular Ca2+ uptake by the kidney. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Beggs, M. R., Appel, I., Svenningsen, P., Skjodt, K., Alexander, R. T., Dimke, H. Tags: RESEARCH ARTICLE Source Type: research
Reduction in podocyte SIRT1 accelerates kidney injury in aging mice
Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury. We emplo...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Chuang, P. Y., Cai, W., Li, X., Fang, L., Xu, J., Yacoub, R., He, J. C., Lee, K. Tags: RESEARCH ARTICLE Source Type: research
Endothelial marker-expressing stromal cells are critical for kidney formation
Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development. To that end, we conditionally deleted Flk1 (critical for endothelial cell d...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Mukherjee, E., Maringer, K., Papke, E., Bushnell, D., Schaefer, C., Kramann, R., Ho, J., Humphreys, B. D., Bates, C., Sims-Lucas, S. Tags: RESEARCH ARTICLE Source Type: research
Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1{beta}
Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1β produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into five groups: 1) control, 2) sham, 3) BOO + vehicle, 4) BOO + the NLRP3 inhibitor glyburide, or 5) BOO + the IL-1β receptor antagonist anakinra. Fibrosis was assessed by Masson’s trichrome stain...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Hughes, F. M., Sexton, S. J., Jin, H., Govada, V., Purves, J. T. Tags: RESEARCH ARTICLE Source Type: research
The sulfilimine cross-link of collagen IV contributes to kidney tubular basement membrane stiffness
Basement membranes (BMs), a specialized form of extracellular matrix, underlie nearly all cell layers and provide structural support for tissues and interact with cell surface receptors to determine cell behavior. Both macromolecular composition and stiffness of the BM influence cell-BM interactions. Collagen IV is a major constituent of the BM that forms an extensively cross-linked oligomeric network. Its deficiency leads to BM mechanical instability, as observed with glomerular BM in Alport syndrome. These findings have led to the hypothesis that collagen IV and its cross-links determine BM stiffness. A sulfilimine bond ...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Bhave, G., Colon, S., Ferrell, N. Tags: RESEARCH ARTICLE Source Type: research
The transcriptome of the Didelphis virginiana opossum kidney OK proximal tubule cell line
The OK cell line derived from the kidney of a female opossum Didelphis virginiana has proven to be a useful model in which to investigate the unique regulation of ion transport and membrane trafficking mechanisms in the proximal tubule (PT). Sequence data and comparison of the transcriptome of this cell line to eutherian mammal PTs would further broaden the utility of this culture model. However, the genomic sequence for D. virginiana is not available and although a draft genome sequence for the opossum Monodelphis domestica (sequenced in 2012 by the Broad Institute) exists, transcripts sequenced from both species show sig...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Eshbach, M. L., Sethi, R., Avula, R., Lamb, J., Hollingshead, D. J., Finegold, D. N., Locker, J. D., Chandran, U. R., Weisz, O. A. Tags: RESEARCH ARTICLE Source Type: research
Combining new tools to assess renal function and morphology: a holistic approach to study the effects of aging and a congenital nephron deficit
Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10–50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of ...
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Geraci, S., Chacon-Caldera, J., Cullen-McEwen, L., Schad, L. R., Sticht, C., Puelles, V. G., Bertram, J. F., Gretz, N. Tags: RESEARCH ARTICLE Source Type: research
Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis
In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - September 1, 2017 Category: Urology & Nephrology Authors: Ding, H., Jiang, L., Xu, J., Bai, F., Zhou, Y., Yuan, Q., Luo, J., Zen, K., Yang, J. Tags: RESEARCH ARTICLE Source Type: research
Corrigendum
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Tags: CORRIGENDA Source Type: research
A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis
Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in ...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Colbert, J. F., Ford, J. A., Haeger, S. M., Yang, Y., Dailey, K. L., Allison, K. C., Neudecker, V., Evans, C. M., Richardson, V. L., Brodsky, K. S., Faubel, S., Eltzschig, H. K., Schmidt, E. P., Ginde, A. A. Tags: RESEARCH ARTICLE Source Type: research
Acute exercise does not impair renal function in nondialysis chronic kidney disease patients regardless of disease stage
In conclusion, a single 30-min moderate-intensity aerobic exercise bout does not impair renal function in nondialysis CKD patients, regardless of disease stage, supporting the notion that exercise training can be safe in this disease. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Santana, D. A., Poortmans, J. R., Dorea, E. L., Machado, J. B. d. A., Fernandes, A. L., Sa-Pinto, A. L., Gualano, B., Roschel, H. Tags: RESEARCH ARTICLE Source Type: research
Altered expression and modulation of the two-pore-domain (K2P) mechanogated potassium channel TREK-1 in overactive human detrusor
Detrusor overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. The mechanisms of bladder smooth muscle compliance upon the wall stretch are poorly understood. We previously reported that the function of normal detrusor is regulated by TREK-1, a member of the mechanogated subfamily of two-pore-domain potassium (K2P) channels. In the present study, we aimed to identify the changes in expression and function of TREK-1 channels under pathological conditions associated with DO, evaluate the potential relationship between TREK-1 channels and ...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Pineda, R. H., Nedumaran, B., Hypolite, J., Pan, X.-Q., Wilson, S., Meacham, R. B., Malykhina, A. P. Tags: RESEARCH ARTICLE Source Type: research
Arginase-2 mediates renal ischemia-reperfusion injury
Novel therapeutic interventions for preventing or attenuating kidney injury following ischemia-reperfusion injury (IRI) remain a focus of significant interest. Currently, there are no definitive therapeutic or preventive approaches available for ischemic acute kidney injury (AKI). Our objective is to determine 1) whether renal arginase activity or expression is increased in renal IRI, and 2) whether arginase plays a role in development of renal IRI. The impact of arginase activity and expression on renal damage was evaluated in male C57BL/6J (wild type) and arginase-2 (ARG2)-deficient (Arg2–/–) mice subjected t...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Raup-Konsavage, W. M., Gao, T., Cooper, T. K., Morris, S. M., Reeves, W. B., Awad, A. S. Tags: RESEARCH ARTICLE Source Type: research
Role for reactive oxygen species in flow-stimulated inner medullary collecting duct endothelin-1 production
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow, and ET-1/GAPDH mRNA was assessed. A shear stress of 10 dyn/cm2 for 1 h increased ET-1 mRNA by fourfold compared with no flow (ET-1 flow response). Global NO synthase (NOS) inhibition [NG-nitro-l-argini...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Wheatley, W., Kohan, D. E. Tags: RESEARCH ARTICLE Source Type: research
Gender difference in kidney electrolyte transport. I. Role of AT1a receptor in thiazide-sensitive Na+-Cl- cotransporter activity and expression in male and female mice
We studied gender differences in Na+-Cl– cotransporter (NCC) activity and expression in wild-type (WT) and AT1a receptor knockout (KO) mice. In renal clearance experiments, urine volume (UV), glomerular filtration rate, absolute Na+ (ENa) and K+ (EK), and fractional Na+ (FENa) and K+ excretion were measured and compared at peak changes after bolus intravenous injection of hydrochlorothiazide (HCTZ; 30 mg/kg). In WT, females responded more strongly than males to HCTZ, with larger fractional increases of UV (7.8- vs. 3.4-fold), ENa (11.7- vs. 5.7-fold), FENa (7.9- vs. 4.9-fold), and EK (2.8- vs. 1.4-fold). In contrast,...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Li, J., Hatano, R., Xu, S., Wan, L., Yang, L., Weinstein, A. M., Palmer, L., Wang, T. Tags: REVIEW Source Type: research
