HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells
This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes fro...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Zhang, W., Zhou, X., Yao, Q., Liu, Y., Zhang, H., Dong, Z. Tags: RESEARCH ARTICLE Source Type: research
Distinct roles of arginases 1 and 2 in diabetic nephropathy
The objective of this study was to identify features of DN that are associated specifically with expression of arginase-1 or –2. Elevated urinary albumin excretion rate and plasma urea levels, increases in renal fibronectin mRNA levels, and decreased renal medullary blood flow were associated almost completely and specifically with arginase-2 expression, indicating that arginase-2 selectively mediates major aspects of diabetic renal injury. However, increases in renal macrophage infiltration and renal TNF-α mRNA levels occurred independent of arginase-2 expression but were almost entirely abolished by treatment...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Morris, S. M., You, H., Gao, T., Vacher, J., Cooper, T. K., Awad, A. S. Tags: RESEARCH ARTICLE Source Type: research
Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle
Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 ...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Kim, S.-J., Kim, J.-E., Kim, Y.-W., Kim, J.-Y., Park, S.-Y. Tags: RESEARCH ARTICLE Source Type: research
Stimulation of fibroblast growth factor 23 by metabolic acidosis requires osteoblastic intracellular calcium signaling and prostaglandin synthesis
Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast, leading to decreased bone formation and increased bone resorption. We...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Krieger, N. S., Bushinsky, D. A. Tags: RESEARCH ARTICLE Source Type: research
Urinary renin-angiotensin markers in polycystic kidney disease
In conclusion, this study shows that, despite similar circulating RAAS component levels, higher urinary excretions of angiotensinogen and renin are a unique feature of ADPKD. Future studies should address the underlying mechanism and whether this may contribute to hypertension or disease progression in ADPKD. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Salih, M., Bovee, D. M., Roksnoer, L. C. W., Casteleijn, N. F., Bakker, S. J. L., Gansevoort, R. T., Zietse, R., Danser, A. H. J., Hoorn, E. J. Tags: RESEARCH ARTICLE Source Type: research
Tubuloglomerular feedback responses in offspring of dexamethasone-treated ewes
Via developmental programming, prenatal perturbations, such as exposure to glucocorticoids and maternal malnutrition alter kidney development and contribute to the development of hypertension. To examine the possibility that alterations in tubuloglomerular feedback (TGF) contribute to the development of hypertension in offspring following maternal dexamethasone treatment (Dex) in early gestation, studies were conducted in fetal sheep and lambs. Pregnant ewes were infused with dexamethasone (0.48 mg/h) at 26–28 days gestation. No differences were observed in mean arterial pressure, glomerular filtration rate. or elect...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Turner, A. J., Brown, R. D., Brandon, A. E., Persson, A. E. G., Gibson, K. J. Tags: RESEARCH ARTICLE Source Type: research
Reversible plasticity of detrusor smooth muscle: evidence for a key role of "slipping" actomyosin cross-bridges in the control of urinary bladder compliance
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Eddinger, T. J. Tags: EDITORIAL FOCUS Source Type: research
Do {beta}3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by inhibiting acetylcholine release?
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Okeke, K., Gravas, S., Michel, M. C. Tags: EDITORIAL FOCUS Source Type: research
Renal hemodynamic effects of glucagon-like peptide-1 agonist are mediated by nitric oxide but not prostaglandin
In conclusion, exenatide is a potent renal vasodilator and diuretic in the rat. These effects of exenatide are insensitive to COX inhibition but are mediated, in part, by NO. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Thomson, S. C., Kashkouli, A., Liu, Z. Z., Singh, P. Tags: RESEARCH ARTICLE Source Type: research
Greater transforming growth factor-{beta} in adult female SHR is dependent on blood pressure, but does not account for sex differences in renal T-regulatory cells
In conclusion, although TGF-β promotes circulating Tregs in female SHR, it does not account for the sex difference in renal Tregs in SHR. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Tipton, A. J., Musall, J. B., Crislip, G. R., Sullivan, J. C. Tags: RESEARCH ARTICLE Source Type: research
Dynamic regulation of lysine acetylation: the balance between acetyltransferase and deacetylase activities
Reversible posttranslational modification of proteins is a critically important process in physiological regulation in all tissues, including the kidney. Lysine acetylation occurs in all organisms, including prokaryotes, and is regulated by a balance between the lysine acetyltransferases (adding an acetyl group to the -amino group of a lysine) and deacetylases (removing it). The kidney is an organ rich with acetylated lysines, which map to >2,000 unique histone and nonhistone proteins. However, the functional significance of these modifications remains to be discovered. Here, we have compiled gene lists of the acetyltra...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Hyndman, K. A., Knepper, M. A. Tags: REVIEW Source Type: research
Developing better mouse models to study cisplatin-induced kidney injury
Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been d...
Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Sharp, C. N., Siskind, L. J. Tags: REVIEW Source Type: research
Insulin stimulates uric acid reabsorption via regulating urate transporter 1 and ATP-binding cassette subfamily G member 2
In this study, we aimed to investigate how diabetes and hypoglycemic agents alter the levels of renal urate transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA were increased, suggesting that tubular handling of UA is altered in this model. In the membrane fraction of the kidney, the expression of urate transporter 1 (URAT1) was significantly decreased, whereas that of ATP-binding cassette subfamily G member 2 (ABCG2) was increased, consistent with the increased renal UA clearance. Administration of insulin to the diabetic rats decreased UA excreti...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Toyoki, D., Shibata, S., Kuribayashi-Okuma, E., Xu, N., Ishizawa, K., Hosoyamada, M., Uchida, S. Tags: RESEARCH ARTICLE Source Type: research
The effects of neuromodulation in a novel obese-prone rat model of detrusor underactivity
Obesity is a global epidemic associated with an increased risk for lower urinary tract dysfunction. Inefficient voiding and urinary retention may arise in late-stage obesity when the expulsive force of the detrusor smooth muscle cannot overcome outlet resistance. Detrusor underactivity (DUA) and impaired contractility may contribute to the pathogenesis of nonobstructive urinary retention. We used cystometry and electrical stimulation of peripheral nerves (pudendal and pelvic nerves) to characterize and improve bladder function in urethane-anesthetized obese-prone (OP) and obese-resistant (OR) rats following diet-induced ob...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Gonzalez, E. J., Grill, W. M. Tags: RESEARCH ARTICLE Source Type: research
Effect of endurance training and branched-chain amino acids on the signaling for muscle protein synthesis in CKD model rats fed a low-protein diet
A low-protein diet (LPD) protects against the progression of renal injury in patients with chronic kidney disease (CKD). However, LPD may accelerate muscle wasting in these patients. Both exercise and branched-chain amino acids (BCAA) are known to increase muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway. The aim of this study was to investigate whether endurance exercise and BCAA play a role for increasing muscle protein synthesis in LPD-fed CKD (5/6 nephrectomized) rats. Both CKD and sham rats were pair-fed on LPD or LPD fortified with a BCAA diet (BD), and approximately one-half of...
Source: AJP: Renal Physiology - September 11, 2017 Category: Urology & Nephrology Authors: Yoshida, T., Kakizawa, S., Totsuka, Y., Sugimoto, M., Miura, S., Kumagai, H. Tags: RESEARCH ARTICLE Source Type: research
