Adenosine A receptor blocks the A receptor inhibition of renal Na transport and oxygen consumption.

A high renal oxygen (O ) need is primarily associated with the renal tubular O consumption (VO ) necessary for a high rate of sodium (Na ) transport. Limited O availability leads to increased levels of adenosine, which regulates the kidney via activation of both A and A adenosine receptors (A1R and A2AR, respectively). The relative contributions of A1R and A2AR to the regulation of renal Na transport and VO have not been determined.

Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease.

Enlargement of kidney tubules is a common feature of multiple cystic kidney diseases in humans and mice. However, while some of these pathologies are characterized by cyst expansion and organ enlargement, in others, progressive interstitial fibrosis and kidney atrophy prevail. The Kif3a knockout mouse is an established non-orthologous mouse model of cystic kidney disease.

Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production.

Thrombotic microangiopathy (TMA) is a disorder characterized by microvascular occlusion that can lead to thrombocytopenia, hemolytic anemia, and glomerular damage. Complement activation is the central event in most cases of TMA. Primary forms of TMA are caused by mutations in genes encoding components of the complement or regulators of the complement cascade.

Hedgehog signaling indirectly affects tubular cell survival after obstructive kidney injury.

Hedgehog (Hh) is an evolutionary conserved signaling pathway that has important functions in kidney morphogenesis and adult organ maintenance. Recent work has shown that Hh signaling is reactivated in the kidney after injury and is an important mediator of progressive fibrosis. Pericytes and fibroblasts have been proposed to be the principal cells that respond to Hh ligands, and pharmacological attenuation of Hh signaling has been considered as a possible treatment for fibrosis, but the effect of Hh inhibition on tubular epithelial cells after kidney injury has not been reported.

Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis.

Kidney fibrosis is marked by an epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs). Here we find that, during renal fibrosis, TECs acquire a partial EMT program during which they remain associated with their basement membrane and express markers of both epithelial and mesenchymal cells. The functional consequence of the EMT program during fibrotic injury is an arrest in the G2 phase of the cell cycle and lower expression of several solute and solvent transporters in TECs.

Dual Effect of Adenosine A1 Receptor Activation on Renal O2 Consumption.

The high requirement of O2 in the renal proximal tubule stems from a high rate of Na(+) transport. Adenosine A1 receptor (A1R) activation regulates Na(+) transport in this nephron segment. Thus, the effect of the acute activation and the mechanisms of A1R on the rate of O2 consumption were evaluated.

DINE-1, the highest copy number repeats in Drosophila melanogaster are non-autonomous endonuclease-encoding rolling-circle transposable elements (Helentrons).

Background: The Drosophila INterspersed Elements-1 (DINE-1/INE1) transposable elements (TEs) are the most abundant component of the Drosophila melanogaster genome and have been associated with functional gene duplications. DINE-1 TEs do not encode any proteins (non-autonomous) thus are moved by autonomous partners. The identity of the autonomous partners has been a mystery.

Mutations in ANKS6 cause a nephronophthisis-like phenotype with ESRD.

Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology.

The biophysical and molecular basis of intracellular pH sensing by Na+/H+ exchanger-3.

Epithelial Na(+)/H(+) exchanger-3 (NHE3) transport is fundamental for renal and intestinal sodium reabsorption. Cytoplasmic protons are thought to serve as allosteric modifiers of the exchanger and to trigger its transport through protein conformational change. This effect presupposes an intracellular pH (pHi) dependence of NHE3 activity, although the biophysical and molecular basis of NHE3 pHi sensitivity have not been defined.

DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN.

Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN.

Calcineurin homologous protein: a multifunctional Ca2+-binding protein family.

The calcineurin homologous protein (CHP) belongs to an evolutionarily conserved Ca(2+)-binding protein subfamily. The CHP subfamily is composed of CHP1, CHP2, and CHP3, which in vertebrates share significant homology at the protein level with each other and between other Ca(2+)-binding proteins. The CHP structure consists of two globular domains containing from one to four EF-hand structural motifs (calcium-binding regions composed of two helixes, E and F, joined by a loop), the myristoylation, and nuclear export signals.