Glucocorticoid-induced leucine zipper protein regulates sodium and potassium balance in the distal nephron.


: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.


Kidney Int


Kidney international


Rashmi P,Colussi G,Ng M,Wu X,Kidwai A,Pearce D




Has Abstract


2017-05-01 00:00:00














  • Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney.

    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


    authors: Abe K,Miyazaki M,Koji T,Furusu A,Ozono Y,Harada T,Sakai H,Nakane PK,Kohno S

    更新日期:1998-07-01 00:00:00

  • Down-regulation of VLDL receptor expression in chronic experimental renal failure.

    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


    authors: Vaziri ND,Liang K

    更新日期:1997-03-01 00:00:00

  • Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids.

    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


    authors: Masud T,Young VR,Chapman T,Maroni BJ

    更新日期:1994-04-01 00:00:00

  • CD11b is protective in complement-mediated immune complex glomerulonephritis.

    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


    authors: Alexander JJ,Chaves LD,Chang A,Jacob A,Ritchie M,Quigg RJ

    更新日期:2015-05-01 00:00:00

  • Coordinated down-regulation of NBC-1 and NHE-3 in sodium and bicarbonate loading.

    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


    authors: Amlal H,Chen Q,Greeley T,Pavelic L,Soleimani M

    更新日期:2001-11-01 00:00:00

  • Simultaneous occlusion of Na+ and phosphate by the intestinal brush border membrane Na+/phosphate cotransporter.

    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


    authors: Peerce BE

    更新日期:1996-04-01 00:00:00

  • Von Willebrand factor regulates complement on endothelial cells.

    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


    authors: Noone DG,Riedl M,Pluthero FG,Bowman ML,Liszewski MK,Lu L,Quan Y,Balgobin S,Schneppenheim R,Schneppenheim S,Budde U,James P,Atkinson JP,Palaniyar N,Kahr WH,Licht C

    更新日期:2016-07-01 00:00:00

  • Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation, and a telocyte phenotype.

    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


    authors: Imeri F,Nolan KA,Bapst AM,Santambrogio S,Abreu-Rodríguez I,Spielmann P,Pfundstein S,Libertini S,Crowther L,Orlando IMC,Dahl SL,Keodara A,Kuo W,Kurtcuoglu V,Scholz CC,Qi W,Hummler E,Hoogewijs D,Wenger RH

    更新日期:2019-02-01 00:00:00

  • Effect of acute potassium load on reabsorption in Henle's loop in chronic renal failure in the rat.

    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


    authors: Milanes CL,Jamison RL

    更新日期:1985-06-01 00:00:00

  • Pathogenesis of vascular calcification in chronic kidney disease.

    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


    authors: Cozzolino M,Brancaccio D,Gallieni M,Slatopolsky E

    更新日期:2005-08-01 00:00:00

  • Microangiographic evaluation of the effects of heparin on progressive Masugi nephritis.

    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


    authors: Nakamoto Y,Dohi K,Fujike H,Yuri T,Shinoda A,Takeuchi J

    更新日期:1978-04-01 00:00:00

  • Substrate oxidation by isolated single nephron segments of the rat.

    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


    authors: Klein KL,Wang MS,Torikai S,Davidson WD,Kurokawa K

    更新日期:1981-07-01 00:00:00

  • Elevated urinary excretion of the C5b-9 complex in membranous nephropathy.

    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


    authors: Schulze M,Donadio JV Jr,Pruchno CJ,Baker PJ,Johnson RJ,Stahl RA,Watkins S,Martin DC,Wurzner R,Gotze O

    更新日期:1991-09-01 00:00:00

  • Critical role for osteopontin in diabetic nephropathy.

    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


    authors: Nicholas SB,Liu J,Kim J,Ren Y,Collins AR,Nguyen L,Hsueh WA

    更新日期:2010-04-01 00:00:00

  • Amylin deposition in the kidney of patients with diabetic nephropathy.

    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


    authors: Gong W,Liu ZH,Zeng CH,Peng A,Chen HP,Zhou H,Li LS

    更新日期:2007-07-01 00:00:00

  • Signal regulatory protein-α interacts with the insulin receptor contributing to muscle wasting in chronic kidney disease.

    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


    authors: Thomas SS,Dong Y,Zhang L,Mitch WE

    更新日期:2013-08-01 00:00:00

  • Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease.

    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


    authors: Lo LJ,Go AS,Chertow GM,McCulloch CE,Fan D,Ordoñez JD,Hsu CY

    更新日期:2009-10-01 00:00:00

  • Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways.

    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


    authors: Bajaj A,Ihegword A,Qiu C,Small AM,Wei WQ,Bastarache L,Feng Q,Kember RL,Risman M,Bloom RD,Birtwell DL,Williams H,Shaffer CM,Chen J,Center RG,Denny JC,Rader DJ,Stein CM,Damrauer SM,Susztak K

    更新日期:2020-05-01 00:00:00

  • Multiple patterns of 11 beta-hydroxysteroid dehydrogenase catalytic activity along the mammalian nephron.

    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


    authors: Kenouch S,Coutry N,Farman N,Bonvalet JP

    更新日期:1992-07-01 00:00:00

  • Gut microbiome and kidney stone disease: not just an Oxalobacter story.

    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


    authors: Ticinesi A,Nouvenne A,Meschi T

    更新日期:2019-07-01 00:00:00

  • Innate immune receptors and autophagy: implications for autoimmune kidney injury.

    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


    authors: Anders HJ,Schlondorff DO

    更新日期:2010-07-01 00:00:00

  • Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation.

    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


    authors: Bestard O,Cruzado JM,Lucia M,Crespo E,Casis L,Sawitzki B,Vogt K,Cantarell C,Torras J,Melilli E,Mast R,Martinez-Castelao A,Gomà M,Reinke P,Volk HD,Grinyó JM

    更新日期:2013-12-01 00:00:00

  • Uremic memory: the role of acute kidney injury in long-term outcomes.

    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


    authors: Golestaneh L,Melamed ML,Hostetter TH

    更新日期:2009-10-01 00:00:00

  • Gelatinase A is a glomerular mesangial cell growth and differentiation factor.

    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


    authors: Turck J,Pollock AS,Lovett DH

    更新日期:1997-05-01 00:00:00

  • Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants.

    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


    authors: Gambertoglio JG,Holford NH,Kapusnik JE,Nishikawa R,Saltiel M,Stanik-Lizak P,Birnbaum JL,Hau T,Amend WJ Jr

    更新日期:1984-01-01 00:00:00

  • Changes in bone structure and the muscle-bone unit in children with chronic kidney disease.

    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


    authors: Tsampalieros A,Kalkwarf HJ,Wetzsteon RJ,Shults J,Zemel BS,Foster BJ,Foerster DL,Leonard MB

    更新日期:2013-03-01 00:00:00

  • Renal biopsy findings among Indigenous Australians: a nationwide review.

    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


    authors: Hoy WE,Samuel T,Mott SA,Kincaid-Smith PS,Fogo AB,Dowling JP,Hughson MD,Sinniah R,Pugsley DJ,Kirubakaran MG,Douglas-Denton RN,Bertram JF

    更新日期:2012-12-01 00:00:00

  • Protective role of selectin ligand inhibition in a large animal model of kidney ischemia-reperfusion injury.

    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


    authors: Jayle C,Milinkevitch S,Favreau F,Doucet C,Richer JP,Deretz S,Mauco G,Rabb H,Hauet T

    更新日期:2006-05-01 00:00:00

  • A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis.

    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


    authors: Yang B,Johnson TS,Thomas GL,Watson PF,Wagner B,Furness PN,El Nahas AM

    更新日期:2002-10-01 00:00:00

  • Recombinant human growth hormone exacerbates chronic puromycin aminonucleoside nephropathy in rats.

    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


    authors: Trachtman H,Futterweit S,Schwob N,Maesaka J,Valderrama E

    更新日期:1993-12-01 00:00:00