Impaired urinary osteopontin excretion in Npt2a-/- mice
Mutations in the renal sodium-dependent phosphate cotransporters NPT2a and NPT2c have been reported in patients with renal stone disease and nephrocalcinosis. Oral phosphate supplementation is currently thought to reduce risk by reversing the hypercalciuria, but the exact mechanism remains unclear and the relative contribution of modifiers of mineralization such as osteopontin (Opn) to the formation of renal mineral deposits in renal phosphate wasting disorders has not been studied. We observed a marked decrease of renal gene expression and urinary excretion of Opn in Npt2a–/– mice, a mouse model of these disor...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Caballero, D., Li, Y., Ponsetto, J., Zhu, C., Bergwitz, C. Tags: RESEARCH ARTICLE Source Type: research
SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone
We examined renal Na and K transporters in mice with deletions in the gene encoding the aldosterone-induced protein SGK1. The knockout mice were hyperkalemic, and had altered expression of the subunits of the epithelial Na channel (ENaC). The kidneys showed decreased expression of the cleaved forms of the ENaC subunit, and the fully glycosylated form of the βENaC subunits when animals were fed a high-K diet. Knockout animals treated with exogenous aldosterone also had reduced subunit processing and diminished surface expression of βENaC and ENaC. Expression of the three upstream Na transporters NHE3, NKCC2, and N...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Yang, L., Frindt, G., Lang, F., Kuhl, D., Vallon, V., Palmer, L. G. Tags: RESEARCH ARTICLE Source Type: research
A kidney-selective biopolymer for targeted drug delivery
Improving drug delivery to the kidney using renal-targeted therapeutics is a promising but underdeveloped area. We aimed to develop a kidney-targeting construct for renal-specific drug delivery. Elastin-like polypeptides (ELPs) are nonimmunogenic protein-based carriers that can stabilize attached small-molecule and peptide therapeutics. We modified ELP at its NH2-terminus with a cyclic, seven-amino acid kidney-targeting peptide (KTP) and at its COOH-terminus with a cysteine residue for tracer conjugation. Comparative in vivo pharmacokinetics and biodistribution in rat and swine models and in vitro cell binding studies usin...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Bidwell, G. L., Mahdi, F., Shao, Q., Logue, O. C., Waller, J. P., Reese, C., Chade, A. R. Tags: RESEARCH ARTICLE Source Type: research
Inflammation drives renal scarring in experimental pyelonephritis
Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis co...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Li, B., Haridas, B., Jackson, A. R., Cortado, H., Mayne, N., Kohnken, R., Bolon, B., McHugh, K. M., Schwaderer, A. L., Spencer, J. D., Ching, C. B., Hains, D. S., Justice, S. S., Partida-Sanchez, S., Becknell, B. Tags: RESEARCH ARTICLE Source Type: research
Crucial roles of nitric oxide synthases in {beta}-adrenoceptor-mediated bladder relaxation in mice
We examined the roles of NOSs in β-adrenoceptor (AR)-mediated bladder relaxation. Male mice (C57BL6) deficient of neuronal NOS [nNOS-knockout (KO)], endothelial NOS (eNOS-KO), neuronal/endothelial NOS (n/eNOS-KO), neuronal/endothelial/inducible NOS (n/e/iNOS-KO), and their controls [wild-type (WT)] were used. Immunohistochemical analysis was performed in the bladder. Then the responses to relaxing agents and the effects of several inhibitors on the relaxing responses were examined in bladder strips precontracted with carbachol. Immunofluorescence staining showed expressions of nNOS and eNOS in the urothelium and smoot...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Satake, Y., Satoh, K., Nogi, M., Omura, J., Godo, S., Miyata, S., Saito, H., Tanaka, S., Ikumi, Y., Yamashita, S., Kaiho, Y., Tsutsui, M., Arai, Y., Shimokawa, H. Tags: RESEARCH ARTICLE Source Type: research
Mesenchymal stem cells protect against obstruction-induced renal fibrosis by decreasing STAT3 activation and STAT3-dependent MMP-9 production
STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase-9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 x 106/rat) immediately before sham operation or induction of unilateral ureteral obstruction (UUO). The kidneys were harvested after 4 wk and analyzed for collagen I and III gene expressi...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Matsui, F., Babitz, S. A., Rhee, A., Hile, K. L., Zhang, H., Meldrum, K. K. Tags: RESEARCH ARTICLE Source Type: research
Physiological roles of claudins in kidney tubule paracellular transport
The paracellular pathways in renal tubular epithelia such as the proximal tubules, which reabsorb the largest fraction of filtered solutes and water and are leaky epithelia, are important routes for transepithelial transport of solutes and water. Movement occurs passively via an extracellular route through the tight junction between cells. The characteristics of paracellular transport vary among different nephron segments with leaky or tighter epithelia. Claudins expressed at tight junctions form pores and barriers for paracellular transport. Claudins are from a multigene family, comprising at least 27 members in mammals. ...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Muto, S. Tags: REVIEW Source Type: research
Ironing out the cross talk between FGF23 and inflammation
The bone-secreted hormone fibroblast growth factor 23 (FGF23) has an essential role in phosphate homeostasis by regulating expression of the kidney proximal tubule sodium-phosphate cotransporters as well as parathyroid hormone levels. Induction of FGF23 early in chronic kidney disease (CKD) helps to maintain normal phosphorous levels. However, high FGF23 levels become pathological as kidney disease progresses and are associated with an increased risk of CKD progression, cardiovascular events, and death. The factors responsible for increasing FGF23 levels early in CKD are unknown, but recent work has proposed a role for inf...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: David, V., Francis, C., Babitt, J. L. Tags: REVIEW Source Type: research
Comment on osmotically inactive ions
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Wolf, M. B. Tags: LETTERS TO THE EDITOR Source Type: research
Inconsistent blood pressure phenotype in female Dahl salt-sensitive rats
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Zimmerman, M. A., Lindsey, S. H. Tags: LETTERS TO THE EDITOR Source Type: research
A computational model for simulating solute transport and oxygen consumption along the nephrons
The goal of this study was to investigate water and solute transport, with a focus on sodium transport (TNa) and metabolism along individual nephron segments under differing physiological and pathophysiological conditions. To accomplish this goal, we developed a computational model of solute transport and oxygen consumption (QO2) along different nephron populations of a rat kidney. The model represents detailed epithelial and paracellular transport processes along both the superficial and juxtamedullary nephrons, with the loop of Henle of each model nephron extending to differing depths of the inner medulla. We used the mo...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Layton, A. T., Vallon, V., Edwards, A. Tags: ARTICLES Source Type: research
Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice
In the setting of normal kidney function, iron deficiency is associated with increased FGF23 production and cleavage, altering circulating FGF23 levels. Our objective was to determine how chronic kidney disease (CKD) and dietary iron intake affect FGF23 production and metabolism in wild-type (WT) and hepcidin knockout (HKO) mice. For 8 wk, the mice were fed diets that contained adenine (to induce CKD) or no adenine (control group), with either low-iron (4 ppm) or standard-iron (335 ppm) concentrations. The low-iron diet induced iron deficiency anemia in both the WT and HKO mice. Among the WT mice, in both the control and C...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Hanudel, M. R., Chua, K., Rappaport, M., Gabayan, V., Valore, E., Goltzman, D., Ganz, T., Nemeth, E., Salusky, I. B. Tags: ARTICLES Source Type: research
Hydrogen peroxide suppresses TRPM4 trafficking to the apical membrane in mouse cortical collecting duct principal cells
A Ca2+-activated nonselective cation channel (NSCCa) is found in principal cells of the mouse cortical collecting duct (CCD). However, the molecular identity of this channel remains unclear. We used mpkCCDc14 cells, a mouse CCD principal cell line, to determine whether NSCCa represents the transient receptor potential (TRP) channel, the melastatin subfamily 4 (TRPM4). A Ca2+-sensitive single-channel current was observed in inside-out patches excised from the apical membrane of mpkCCDc14 cells. Like TRPM4 channels found in other cell types, this channel has an equal permeability for Na+ and K+ and has a linear current-volta...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Wu, M.-M., Zhai, Y.-J., Li, Y.-X., Hu, Q.-Q., Wang, Z.-R., Wei, S.-P., Zou, L., Alli, A. A., Thai, T. L., Zhang, Z.-R., Ma, H.-P. Tags: ARTICLES Source Type: research
Environmental hit on a genetic basis in polycystic kidney disease
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Wang, S., Dong, Z. Tags: EDITORIAL FOCUS Source Type: research
ILK and cytoskeletal architecture: an important determinant of AQP2 recycling and subsequent entry into the exocytotic pathway
Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, to open a path toward effective diabetes insipidus therapeutics. A recent study has shown that integrin-linked kinase (ILK) conditional-knockdown mice developed polyuria along with decreased AQP2 expression. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells). Upon treatment of LLC-AQP2 cells with ILK inhibitor cpd22 and ILK-siRNA, we observed increas...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Mamuya, F. A., Cano-Penalver, J. L., Li, W., Rodriguez Puyol, D., Rodriguez Puyol, M., Brown, D., de Frutos, S., Lu, H. A. J. Tags: CALL FOR PAPERS Source Type: research
