Role of TGF-alpha in the progression of diabetic kidney disease
Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circ...
Source: AJP: Renal Physiology - June 1, 2017 Category: Urology & Nephrology Authors: Heuer, J. G., Harlan, S. M., Yang, D. D., Jaqua, D. L., Boyles, J. S., Wilson, J. M., Heinz-Taheny, K. M., Sullivan, J. M., Wei, T., Qian, H.-R., Witcher, D. R., Breyer, M. D. Tags: RESEARCH ARTICLE Source Type: research
A mathematical model of the rat kidney: K+-induced natriuresis
A model of the rat nephron (Weinstein. Am J Physiol Renal Physiol 308: F1098–F1118, 2015) has been extended with addition of medullary vasculature. Blood vessels contain solutes from the nephron model, plus additional species from the model of Atherton et al. (Am J Physiol Renal Fluid Electrolyte Physiol 247: F61–F72, 1984), representing hemoglobin buffering. In contrast to prior models of the urine-concentrating mechanism, reflection coefficients for DVR are near zero. Model unknowns are initial proximal tubule pressures and flows, connecting tubule pressure, and medullary interstitial pressures and concentrat...
Source: AJP: Renal Physiology - June 1, 2017 Category: Urology & Nephrology Authors: Weinstein, A. M. Tags: RESEARCH ARTICLE Source Type: research
Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease
Chronic kidney disease (CKD) patients have exercise intolerance associated with increased cardiovascular mortality. Previous studies demonstrate that blood pressure (BP) and sympathetic nerve responses to handgrip exercise are exaggerated in CKD. These patients also have decreased nitric oxide (NO) bioavailability and endothelial dysfunction, which could potentially lead to an impaired ability to vasodilate during exercise. We hypothesized that CKD patients have exaggerated BP responses during maximal whole body exercise and that endothelial dysfunction correlates with greater exercise pressor responses in these patients. ...
Source: AJP: Renal Physiology - May 15, 2017 Category: Urology & Nephrology Authors: Downey, R. M., Liao, P., Millson, E. C., Quyyumi, A. A., Sher, S., Park, J. Tags: RESEARCH ARTICLE Source Type: research
Myoglobin facilitates angiotensin II-induced constriction of renal afferent arterioles
In conclusion, myoglobin may contribute to the afferent arteriolar vasoconstriction in this rhabdomyolysis model. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - May 15, 2017 Category: Urology & Nephrology Authors: Liu, Z. Z., Mathia, S., Pahlitzsch, T., Wennysia, I. C., Persson, P. B., Lai, E. Y., Högner, A., Xu, M. Z., Schubert, R., Rosenberger, C., Patzak, A. Tags: RESEARCH ARTICLE Source Type: research
Endothelial colony-forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury
Damage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFC) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFC may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia-reperfusion (I/R). Rat pulmonary microvascular endothelial cells (PMVEC) with high proliferative potential were compared with pulmonary artery endothelial cells (PAEC) with low proliferative potential in rats subjected to renal I/R. ...
Source: AJP: Renal Physiology - May 15, 2017 Category: Urology & Nephrology Authors: Collett, J. A., Mehrotra, P., Crone, A., Shelley, W. C., Yoder, M. C., Basile, D. P. Tags: RESEARCH ARTICLE Source Type: research
Path of translational discovery of urological complications of obesity and diabetes
Diabetes mellitus (DM) is a prevalent chronic disease. Type 1 DM (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin, whereas type 2 DM (T2DM) is due to insulin resistance-related relative insulin deficiency. In comparison with T1DM, T2DM is more complex. The natural history of T2DM in most patients typically involves a course of obesity to impaired glucose tolerance, to insulin resistance, to hyperinsulinemia, to hyperglycemia, and finally to insulin deficiency. Obesity is a risk factor of T2DM. Diabetes causes some serious microvascular and macrovascular compli...
Source: AJP: Renal Physiology - May 15, 2017 Category: Urology & Nephrology Authors: Daneshgari, F., Liu, G., Hanna-Mitchell, A. T. Tags: REVIEW Source Type: research
Angiotensinogen import in isolated proximal tubules: evidence for mitochondrial trafficking and uptake
The renal proximal tubules are a key functional component of the kidney and express the angiotensin precursor angiotensinogen; however, it is unclear the extent that tubular angiotensinogen reflects local synthesis or internalization. Therefore, the current study established the extent to which angiotensinogen is internalized by proximal tubules and the intracellular distribution. Proximal tubules were isolated from the kidney cortex of male sheep by enzymatic digestion and a discontinuous Percoll gradient. Tubules were incubated with radiolabeled 125I-angiotensinogen for 2 h at 37°C in serum/phenol-free DMEM/F12 media...
Source: AJP: Renal Physiology - May 3, 2017 Category: Urology & Nephrology Authors: Wilson, B. A., Cruz-Diaz, N., Su, Y., Rose, J. C., Gwathmey, T. M., Chappell, M. C. Tags: RESEARCH ARTICLE Source Type: research
Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans
Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 μg·kg–1·min–1 NG-nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-i...
Source: AJP: Renal Physiology - May 3, 2017 Category: Urology & Nephrology Authors: Montanari, A., Lazzeroni, D., Pela, G., Crocamo, A., Lytvyn, Y., Musiari, L., Cabassi, A., Cherney, D. Z. I. Tags: RESEARCH ARTICLE Source Type: research
Renal inflammation and injury are associated with lymphangiogenesis in hypertension
Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation; however, it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at 40 wk of age comp...
Source: AJP: Renal Physiology - May 3, 2017 Category: Urology & Nephrology Authors: Kneedler, S. C., Phillips, L. E., Hudson, K. R., Beckman, K. M., Lopez Gelston, C. A., Rutkowski, J. M., Parrish, A. R., Doris, P. A., Mitchell, B. M. Tags: RESEARCH ARTICLE Source Type: research
Secretin, at the hub of water-salt homeostasis
Water and salt metabolism are tightly regulated processes. Maintaining this milieu intérieur within narrow limits is critical for normal physiological processes to take place. Disturbances to this balance can result in disease and even death. Some of the better-characterized regulators of water and salt homeostasis include angiotensin II, aldosterone, arginine vasopressin, and oxytocin. Although secretin (SCT) was first described >100 years ago, little is known about the role of this classic gastrointestinal hormone in the maintenance of water-salt homeostasis. In recent years, increasing body of evidence suggest...
Source: AJP: Renal Physiology - May 3, 2017 Category: Urology & Nephrology Authors: Bai, J. J., Tan, C. D., Chow, B. K. C. Tags: REVIEW Source Type: research
Corrigendum
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - April 20, 2017 Category: Urology & Nephrology Tags: CORRIGENDA Source Type: research
Inhibition of vascular smooth muscle inward-rectifier K+ channels restores myogenic tone in mouse urinary bladder arterioles
Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5–80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (–72.8 ± 1.4 mV) at 20 mmHg and unaf...
Source: AJP: Renal Physiology - April 20, 2017 Category: Urology & Nephrology Authors: Tykocki, N. R., Bonev, A. D., Longden, T. A., Heppner, T. J., Nelson, M. T. Tags: RESEARCH ARTICLE Source Type: research
Primary proximal tubule hyperreabsorption and impaired tubular transport counterregulation determine glomerular hyperfiltration in diabetes: a modeling analysis
Glomerular hypertension and hyperfiltration in early diabetes are associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (PBow). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response. The model implicates that the primary hyper...
Source: AJP: Renal Physiology - April 20, 2017 Category: Urology & Nephrology Authors: Hallow, K. M., Gebremichael, Y., Helmlinger, G., Vallon, V. Tags: RESEARCH ARTICLE Source Type: research
Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes
In this study, we present the first RNASeq analysis of a Pkd1-mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD Signature, a set of 1,515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions. Moreover, genes with a role in injury repair, as evidenced by expression data and/or automated literature analysis, were significantly enriched in the PKD Signature, with 35% of the PKD Signature genes being directly implicated in injury repair. NF-B signaling, epithelial-mesench...
Source: AJP: Renal Physiology - April 7, 2017 Category: Urology & Nephrology Authors: Malas, T. B., Formica, C., Leonhard, W. N., Rao, P., Granchi, Z., Roos, M., Peters, D. J. M., 't Hoen, P. A. C. Tags: RESEARCH ARTICLE Source Type: research
