Abstract:
:Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz-/- mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice. Furthermore, knockout mice are more sensitive to NCC inhibition by thiazides than are the wild type mice, and their phosphorylated NCC expression is higher. Despite increased NCC activity, knockout mice do not have higher blood pressure than wild type mice. However, during sodium deprivation, knockout mice come into sodium balance more quickly, than do the wild type, without a significant increase in plasma renin activity. Upon prolonged sodium restriction, knockout mice develop frank hyperkalemia. Finally, in HEK293T cells, exogenous GILZ inhibits NCC activity at least in part by inhibiting SPAK phosphorylation. Thus, GILZ promotes potassium secretion by inhibiting NCC and enhancing distal sodium delivery to the epithelial sodium channel. Additionally, Gilz-/- mice have features resembling familial hyperkalemic hypertension, a human disorder that manifests with hyperkalemia associated variably with hypertension.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Rashmi P,Colussi G,Ng M,Wu X,Kidwai A,Pearce Ddoi
10.1016/j.kint.2016.10.038subject
Has Abstractpub_date
2017-05-01 00:00:00pages
1159-1177issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30654-8journal_volume
91pub_type
杂志文章abstract:BACKGROUND:Decay accelerating factor (DAF), a product of mesangial cells in vitro, is expressed on the surface of cells and is a candidate for the focal suppression of complement activation. It is not clear at present whether the levels of expression of DAF and intrarenal C3 synthesis correlate with the level of tissue...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00961.x
更新日期:1998-07-01 00:00:00
abstract::VLDL receptor (VLDL-R) is a novel member of the LDL receptor gene family with distinct tissue distribution and function. It binds and internalizes VLDL particles and is primarily expressed in skeletal muscle, heart, brain and adipose tissue, which use fatty acids for energy production or storage. CRF is associated wit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.129
更新日期:1997-03-01 00:00:00
abstract::Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days b...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1994.157
更新日期:1994-04-01 00:00:00
abstract::In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.373
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00995.x
更新日期:2001-11-01 00:00:00
abstract::The molecular mechanism of Na+ and phosphate transport by the intestinal brush border membrane Na+/phosphate cotransporter was examined using anion and cation exchange columns interfaced to a light-activated microsecond timer. The nature of ion:cotransporter interaction was examined for sensitivity to itself versus no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.141
更新日期:1996-04-01 00:00:00
abstract::Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have traditionally been considered separate entities. Defects in the regulation of the complement alternative pathway occur in atypical hemolytic uremic syndrome, and defects in the cleavage of von Willebrand factor (VWF)-multimers arise in thr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.03.023
更新日期:2016-07-01 00:00:00
abstract::Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.08.043
更新日期:2019-02-01 00:00:00
abstract::To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and af...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.100
更新日期:1985-06-01 00:00:00
abstract::Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the pro...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00421.x
更新日期:2005-08-01 00:00:00
abstract::Unilateral progressive Masugi nephritis was produced in rabbits and studied by microangiography as well as light and immunofluorescence microscopy. The following five groups were studied: Group 1. Heparin was started simultaneously with nephrotoxic serum (NTS) and was given for one week. The animals were then sacrific...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.43
更新日期:1978-04-01 00:00:00
abstract::Substrate oxidation was assessed by measuring 14CO2 production from 14C-labeled substrates in proximal convoluted tubules (PCT), medullary (MTAL), and cortical (CTAL) thick ascending limb of Henle, nephron segments rich in mitochondria and characterized by active solute transport. PCT, MTAL, and CTAL were dissected fr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.100
更新日期:1981-07-01 00:00:00
abstract::In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.242
更新日期:1991-09-01 00:00:00
abstract::The profibrotic adhesion molecule, osteopontin (OPN), is upregulated in kidneys of humans and mice with diabetes. The thiazolidinedione (TZD) insulin sensitizers decrease albuminuria in diabetic nephropathy (DN) and reduce OPN expression in vascular and cardiac tissue. To examine whether OPN is a critical mediator of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.518
更新日期:2010-04-01 00:00:00
abstract::Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in the development of beta-cell dysfunction in patients with diabetes; however, the involvement of amylin in renal amyloidosis has not been studied. For this reason, we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002305
更新日期:2007-07-01 00:00:00
abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract::To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.289
更新日期:2009-10-01 00:00:00
abstract::The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.027
更新日期:2020-05-01 00:00:00
abstract::The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.260
更新日期:1992-07-01 00:00:00
abstract::Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming cont...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.03.020
更新日期:2019-07-01 00:00:00
abstract::Inflammation is the immune system's response to infectious or noninfectious sources of danger. Danger recognition is facilitated by various innate immune receptor families including the Toll-like receptors (TLRs), which detect danger signals in extracellular and intracellular compartments. It is an evolving concept th...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2010.111
更新日期:2010-07-01 00:00:00
abstract::Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.236
更新日期:2013-12-01 00:00:00
abstract::Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when p...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.314
更新日期:2009-10-01 00:00:00
abstract::The members of the matrix metalloproteinase gene family play critical roles in numerous physiologic events, including cellular migration, tissue remodeling in wound healing and development, as well as in the evolution of the inflammatory process. The 72 kDa gelatinase A (formerly denoted 72 kDa Type IV collagenase) is...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1997.191
更新日期:1997-05-01 00:00:00
abstract::Kidney transplant patients receiving phenytoin or phenobarbital may have decreased graft survival. These drugs have been shown to enhance the metabolism of glucocorticoids. We determined the disposition of total and unbound prednisolone in six stable kidney transplant patients receiving prednisone for immunosuppressio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.17
更新日期:1984-01-01 00:00:00
abstract::The impact of pediatric chronic kidney disease (CKD) on acquisition of volumetric bone mineral density (BMD) and cortical dimensions is lacking. To address this issue, we obtained tibia quantitative computed tomography scans from 103 patients aged 5-21 years with CKD (26 on dialysis) at baseline and 12 months later. G...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.347
更新日期:2013-03-01 00:00:00
abstract::Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathologic...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2012.307
更新日期:2012-12-01 00:00:00
abstract::Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000335
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Although apoptosis has been linked to the renal cell deletion and ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio. However, its importance in controlling apoptosis in glomerulonephritis is unclear. Here, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid587.x
更新日期:2002-10-01 00:00:00
abstract::Growth failure is a cardinal feature of chronic renal failure in children. Administration of recombinant human growth hormone (rhGH) ameliorates this problem but may adversely affect the kidney and hasten the progression to end-stage renal disease. We conducted experiments to examine the impact of rhGH on the severity...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.380
更新日期:1993-12-01 00:00:00