Outside the mainstream: novel collecting duct proteins regulating water balance
Body water balance is critical to survival and, therefore, very tightly regulated by the hypothalamus and kidney. A key mechanism involved in this process, the arginine vasopressin-mediated phosphorylation and apical membrane insertion of aquaporin 2 in the collecting duct, has been extensively studied; however, with the increased availability of conditional knockout animals, several novel collecting duct proteins have recently been implicated in water homeostasis. In this Mini-Review, we briefly discuss these novel proteins and their roles in the regulation of water homeostasis. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Rahman, S. S., Boesen, E. I. Tags: MINI-REVIEW Source Type: research
Downregulation of kidney protective factors by inflammation: role of transcription factors and epigenetic mechanisms
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression, and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD, and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR). Klotho has anti-aging and nephroprotective properties, and decreased Klotho levels may co...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Ruiz-Andres, O., Sanchez-Nino, M. D., Moreno, J. A., Ruiz-Ortega, M., Ramos, A. M., Sanz, A. B., Ortiz, A. Tags: REVIEWS Source Type: research
Molecular mechanisms regulating aquaporin-2 in kidney collecting duct
The kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone that induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of the Aqp2 gene to increase AQP2 protein abundance. The signaling pathways, including...
Source: AJP: Renal Physiology - December 11, 2016 Category: Urology & Nephrology Authors: Jung, H. J., Kwon, T.-H. Tags: REVIEWS Source Type: research
Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress
Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Raij, L., Tian, R., Wong, J. S., He, J. C., Campbell, K. N. Tags: ARTICLES Source Type: research
Depletion of vacuolar protein sorting-associated protein 35 is associated with increased lysosomal degradation of aquaporin-2
The carboxyl terminus of aquaporin-2 (AQP2c) undergoes posttranslational modifications, including phosphorylation and ubiquitination, in the process of regulating aquaporin-2 (AQP2) translocation and protein abundance. We aimed to identify novel proteins interacting with AQP2c. Recombinant AQP2c protein was made in Escherichia coli BL21 (DE3) cells by exploiting the pET32 TrxA fusion system. Lysates of rat kidney inner medullary collecting duct (IMCD) tubule suspensions interacted with rat AQP2c bound to Ni2+-resin were subjected to LC-MS/MS proteomic analysis. Potential interacting proteins were identified, including vacu...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Lee, M. S., Choi, H.-J., Park, E.-J., Park, H.-J., Kwon, T.-H. Tags: ARTICLES Source Type: research
Structural determinants of NH3 and NH4+ transport by mouse Rhbg, a renal Rh glycoprotein
Renal Rhbg is localized to the basolateral membrane of intercalated cells and is involved in NH3/NH4+ transport. The structure of Rhbg is not yet resolved; however, a high-resolution crystal structure of AmtB, a bacterial homolog of Rh, has been determined. We aligned the sequence of Rhbg to that of AmtB and identified important sites of Rhbg that may affect transport. Our analysis positioned three conserved amino acids, histidine 183 (H183), histidine 342 (H342), and tryptophan 230 (W230), within the hydrophobic pore where they presumably serve to control NH3 transport. A fourth residue, phenylalanine 128 (F128) was posit...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Abdulnour-Nakhoul, S., Le, T., Rabon, E., Hamm, L. L., Nakhoul, N. L. Tags: ARTICLES Source Type: research
Proteinuria causes dysfunctional autophagy in the proximal tubule
Proteinuria is a major risk factor for chronic kidney disease progression. Furthermore, exposure of proximal tubular epithelial cells to excess albumin promotes tubular atrophy and fibrosis, key predictors of progressive organ dysfunction. However, the link between proteinuria and tubular damage is unclear. We propose that pathological albumin exposure impairs proximal tubular autophagy, an essential process for recycling damaged organelles and toxic intracellular macromolecules. In both mouse primary proximal tubule and immortalized human kidney cells, albumin exposure decreased the number of autophagosomes, visualized by...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Nolin, A. C., Mulhern, R. M., Panchenko, M. V., Pisarek-Horowitz, A., Wang, Z., Shirihai, O., Borkan, S. C., Havasi, A. Tags: ARTICLES Source Type: research
What we need to know about renal nerve ablation for treatment of hypertension and other states of sympathetic overactivity
Renal nerves are key players in the regulation of kidney function and blood pressure control. Targeting the neurogenic mechanisms underlying hypertension and cardiac and renal disease has been attempted by means of surgical and pharmacologic approaches and most recently by catheter-based interventions aimed at disrupting renal sympathetic nerve traffic. The recent developments in the area and the relevant questions that need to be addressed to advance the field further are briefly reviewed in this article. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Schlaich, M. P. Tags: PERSPECTIVES Source Type: research
Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO
Diets rich in grains and meat and low in fruits and vegetables (acid-producing diets) associate with incident hypertension, whereas vegetarian diets associate with lower blood pressure (BP). However, the pathways that sense and mediate the effects of acid-producing diets on BP are unknown. Here, we examined the impact of the deletion of an acid sensor GPR4 on BP. GPR4 is a proton-sensing G protein-coupled receptor and an acid sensor in brain, kidney, and blood vessels. We found that GPR4 mRNA was higher in subfornical organ (SFO) than other brain regions. GPR4 protein was abundant in SFO and present in capillaries througho...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Sun, X., Tommasi, E., Molina, D., Sah, R., Brosnihan, K. B., Diz, D., Petrovic, S. Tags: RAPID REPORTS Source Type: research
Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels
In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Hristov, K. L., Parajuli, S. P., Provence, A., Petkov, G. V. Tags: CALL FOR PAPERS Source Type: research
Genetic, pathophysiological, and clinical aspects of nephrocalcinosis
Nephrocalcinosis describes the ectopic deposition of calcium salts in the kidney parenchyma. Nephrocalcinosis can result from a number of acquired causes but also an even greater number of genetic diseases, predominantly renal but also extrarenal. Here we provide a review of the genetic causes of nephrocalcinosis, along with putative mechanisms, illustrated by human and animal data. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Oliveira, B., Kleta, R., Bockenhauer, D., Walsh, S. B. Tags: REVIEWS Source Type: research
Maintenance of vascular integrity by pericytes is essential for normal kidney function
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Los...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Lemos, D. R., Marsh, G., Huang, A., Campanholle, G., Aburatani, T., Dang, L., Gomez, I., Fisher, K., Ligresti, G., Peti-Peterdi, J., Duffield, J. S. Tags: ARTICLES Source Type: research
Solute transport and oxygen consumption along the nephrons: effects of Na+ transport inhibitors
Sodium and its associated anions are the major determinant of extracellular fluid volume, and the reabsorption of Na+ by the kidney plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and TNa efficiency and how those effects may vary along different nephron segments. To accomplish that goal, we used the multinephron model developed in the companion study (28). That model represents detailed transcellular and paracellular transport processes along the nephrons...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Layton, A. T., Laghmani, K., Vallon, V., Edwards, A. Tags: ARTICLES Source Type: research
Quantification of intact plasma AGT consisting of oxidized and reduced conformations using a modified ELISA
The pleiotropic actions of the renin-angiotensin system (RAS) depend on the availability of angiotensinogen (AGT) which generates angiotensin I (ANG I) when cleaved by renin. Thus, quantification of the intact AGT (iAGT) concentrations is important to evaluate the actual renin substrate available. The iAGT conformation exists as oxidized AGT (oxi-AGT) and reduced AGT (red-AGT) in a disulfide bond, and oxi-AGT has a higher affinity for renin, which may exacerbate RAS-associated diseases. Accordingly, we determined iAGT, oxi-AGT, and red-AGT levels in plasma from rats and mice. Blood samples were obtained by cardiac puncture...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Satou, R., Kobori, H., Katsurada, A., Miyata, K., Navar, L. G. Tags: ARTICLES Source Type: research
Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase
Activation of the thick ascending limb (TAL) Na+-K+-2Cl– cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET l...
Source: AJP: Renal Physiology - November 30, 2016 Category: Urology & Nephrology Authors: Boldt, C., Röschel, T., Himmerkus, N., Plain, A., Bleich, M., Labes, R., Blum, M., Krause, H., Magheli, A., Giesecke, T., Mutig, K., Rothe, M., Weldon, S. M., Dragun, D., Schunck, W.-H., Bachmann, S., Paliege, A. Tags: ARTICLES Source Type: research
