SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation.

SIRT7 is a NAD -dependent deacetylase that controls important aspects of metabolism, cancer, and bone formation. However, the molecular targets and functions of SIRT7 in the kidney are currently unknown. In silico analysis of kidney transcripts of the BXD murine genetic reference population revealed a positive correlation between Sirt7 and Slc12a7 mRNA expression, suggesting a link between the corresponding proteins that these transcripts encode, SIRT7, and the K-Cl cotransporter KCC4, respectively.

Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease.

Background: Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous coenzyme involved in electron transport and a co-substrate for sirtuin function. NAD+ deficiency has been demonstrated in the context of acute kidney injury (AKI).

Methods: We studied the expression of key NAD+ biosynthesis enzymes in kidney biopsies from human allograft patients and patients with chronic kidney disease (CKD) at different stages.

The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.

Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation.

Klotho regulation by albuminuria is dependent on ATF3 and endoplasmic reticulum stress.

Proteinuria is associated with renal function decline and cardiovascular mortality. This association may be attributed in part to alterations of Klotho expression induced by albuminuria, yet the underlying mechanisms are unclear. The presence of albumin decreased Klotho expression in the POD-ATTAC mouse model of proteinuric kidney disease as well as in kidney epithelial cell lines.

Tubular NOX4 expression decreases in chronic kidney disease but does not modify fibrosis evolution.

Background: NADPH oxidase 4 (NOX4) catalyzes the formation of hydrogen peroxide (HO). NOX4 is highly expressed in the kidney, but its role in renal injury is unclear and may depend on its specific tissue localization.

Methods: We performed immunostaining with a specific anti-NOX4 antibody and measured NOX4 mRNA expression in human renal biopsies encompassing diverse renal diseases.

Potential benefits and harms of NADPH oxidase type 4 in the kidneys and cardiovascular system.

The main function of NADPH oxidases is to catalyse the formation of reactive oxygen species (ROS). NADPH oxidase 4 (NOX4) is expressed at high levels in kidney tubular cells, and at lower levels in endothelial cells, cardiomyocytes and other cell types under physiological conditions. NOX4 is constitutively active producing hydrogen peroxide (H2O2) as the prevalent ROS detected, whereas other NOX isoforms present in the renal and cardiovascular systems (i.

Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.

Adaptation of the organism to potassium (K) deficiency requires precise coordination among organs involved in K homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na/Cl cotransporter (NCC), and with no-lysine-kinase 1 (WNK1).

Extracellular K rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl -dependent and independent mechanisms.

Key Points: High dietary potassium (K ) intake dephosphorylates and inactivates the NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Using several ex vivo models, we show that physiological changes in extracellular K , similar to those occurring after a K rich diet, are sufficient to promote a very rapid dephosphorylation of NCC in native DCT cells. Although the increase of NCC phosphorylation upon decreased extracellular K appears to depend on cellular Cl fluxes, the rapid NCC dephosphorylation in response to increased extracellular K is not Cl -dependent.

Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.

The stimulation of postprandial K(+) clearance involves aldosterone-independent and -dependent mechanisms. In this context, serum- and glucocorticoid-induced kinase (SGK)1, a ubiquitously expressed kinase, is one of the primary aldosterone-induced proteins in the aldosterone-sensitive distal nephron. Germline inactivation of SGK1 suggests that this kinase is fundamental for K(+) excretion under conditions of K(+) load, but the specific role of renal SGK1 remains elusive.

Progesterone and Wnt4 control mammary stem cells via myoepithelial crosstalk.

Ovarian hormones increase breast cancer risk by poorly understood mechanisms. We assess the role of progesterone on global stem cell function by serially transplanting mouse mammary epithelia. Progesterone receptor (PR) deletion severely reduces the regeneration capacity of the mammary epithelium.

Paracrine signaling by progesterone.

Steroid hormones coordinate and control the development and function of many organs and are implicated in many pathological processes. Progesterone signaling, in particular, is essential for several important female reproductive functions. Physiological effects of progesterone are mediated by its cognate receptor, expressed in a subset of cells in target tissues.

Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis.

Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jkappa gene, the effector of "canonical" Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells.

Two distinct mechanisms underlie progesterone-induced proliferation in the mammary gland.

The mouse mammary gland develops postnatally under the control of female reproductive hormones. Estrogens and progesterone trigger morphogenesis by poorly understood mechanisms acting on a subset of mammary epithelial cells (MECs) that express their cognate receptors, estrogen receptor alpha (ERalpha) and progesterone receptor (PR). Here, we show that in the adult female, progesterone drives proliferation of MECs in two waves.

Alveolar and lactogenic differentiation.

The mouse mammary gland is a complex tissue that proliferates and differentiates under the control of systemic hormones during puberty, pregnancy and lactation. Once a highly branched milk duct system has been established, during mid/late pregnancy, alveoli, little saccular outpouchings, sprout all over the ductal system and differentiate to become the sites of milk secretion. Here, we review the emerging network of the signaling pathways that connects hormonal stimuli with locally produced signaling molecules and the components of intracellular pathways that regulate alveologenesis and lactation.