Epithelial sodium channel

Chemoreception is critical for the survival and reproduction of animals. Except for a reduced group of insects and chelicerates, the molecular identity of chemosensory proteins is poorly understood in invertebrates. Gastropoda is the extant mollusk class with the greatest species richness, including marine, freshwater, and terrestrial lineages, and likely, highly diverse chemoreception systems. Here, we performed a comprehensive comparative genome analysis taking advantage of the chromosome-level information of two Gastropoda species, one of which belongs to a lineage that underwent a whole genome duplication event...

Epithelial sodium channel (ENaC) are integral to maintaining salt and water homeostasis in various biological tissues, including the kidney, lung, and colon. They enable the selective reabsorption of sodium ions, which is a process critical for controlling blood pressure, electrolyte balance, and overall fluid volume. ENaC activity is finely controlled through proteolytic activation, a process wherein specific enzymes, or proteases, cleave ENaC subunits, resulting in channel activation and increased sodium reabsorption...

The aim of the current work was to examine for the first time the nephropreventive capacity of Ephedra alata seed extract (E) against maternal exposure to acephate in rat offspring. The in vivo results revealed that E. alata supplementation for 28 days (40 mg/kg b.w.) significantly attenuated the nephrotoxicity in adult offspring induced by acephate. In fact, it decreased the levels of creatinine and uric acid and increased the albumin content compared to the intoxicated group. The in utero studies showed that E...

Deciphering the dynamics of water transport across bronchial epithelial cell monolayers is pivotal for unraveling respiratory physiology and pathology. In this study, we employ an advanced microfluidic system to explore bidirectional water transport across 16HBE14σ bronchial epithelial cells. Previous experiments unveiled electroneutral multiple ion transport, with chloride ions utilizing transcellular pathways and sodium ions navigating both paracellular and transcellular routes. Unexpectedly, under isoosmotic conditions, rapid bidirectional movement of Na+ and Cl- was observed, leading to the hypothesis of a substantial transport of isoosmotic solution (145 mM NaCl) across cell monolayers...

BACKGROUND: In patients with diarrhea-predominant irritable bowel syndrome (IBS-D), the diarrheal mechanisms are largely unknown, and they were examined in this study on colon biopsies. METHODS: Electrophysiological measurements were used for monitoring functional changes in the diarrheic colon specimens. In parallel, tight junction protein expression was analyzed by Western blot and confocal laser-scanning microscopy, and signaling pathway analysis was performed using RNA sequencing and bioinformatics...

Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in SCNN1A , SCNN1B or SCNN1G , which respectively encode the α, β and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole‑exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co‑segregation analysis was conducted...

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a ubiquitously expressed protein belonging to the Ser/Thr kinase family. It regulates diverse physiological processes, including epithelial sodium channel activity, hypertension, cell proliferation, and insulin sensitivity. Due to its significant role in the pathogenesis of numerous diseases, SGK1 can be exploited as a potential therapeutic target to address challenging health problems. SGK1 is associated with the development of obesity, and its overexpression enhances the sodium-glucose co-transporter 1 activity, which absorbs intestinal glucose...

BACKGROUND: Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. METHODS: We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis...

Hypertension is the leading remediable risk factor for cardiovascular morbidity and mortality in the United States. Excess dietary salt consumption, which is a catalyst of hypertension, initiates an inflammatory cascade via activation of antigen-presenting cells (APCs). This pro-inflammatory response is driven primarily by sodium ions (Na+ ) transporting into APCs by the epithelial sodium channel (ENaC) and subsequent NADPH oxidase activation, leading to high levels of oxidative stress. Oxidative stress, a well-known catalyst for hypertension-related illness development, disturbs redox homeostasis, which ultimately promotes lipid peroxidation, isolevuglandin production and an inflammatory response...

BACKGROUND: Non-type-A intercalated cells (IC) in the collecting duct system express the luminal Cl - /HCO 3- exchanger pendrin and apical and/or basolateral H + -ATPases containing the B1 subunit isoform. Non-type-A ICs excrete bicarbonate during metabolic alkalosis. Mutations in the B1 subunit (ATP6V1B1) cause distal renal tubular acidosis due to its role in acid secretory type-A ICs. The function of B1 in non-type-A ICs has remained elusive. METHODS: We examined responses of Atp6v1b1-/- and Atp6v1b1+/+ mice to an alkali load and to chronic treatment with furosemide...

Acute lung injury (ALI) is a progressive inflammatory injury, and mesenchymal stem cells (MSCs) can be used to treat ALI. MSC-conditioned medium (MSC-CM) contains many cytokines, in which keratinocyte growth factor (KGF) is a soluble factor that plays a role in lung development. We aim to explore the protective effects of MSCs secreted KGF on ALI, and investigate the involvement of epithelial sodium channel (ENaC), which are important in alveolar fluid reabsorption. Both lipopolysaccharides (LPS)-induced mouse and alveolar organoid ALI models were established to confirm the potential therapeutic effect of MSCs secreted KGF...

Otitis media is a common disease but can cause severe inner ear inflammation and hearing loss if it persists for more than two weeks. This study elucidates the inflammation-inhibiting efficacy of conditioned medium (CM) and extracellular vesicles (EVs) derived from human trophoblast (TB) cells in lipopolysaccharide (LPS)-induced human middle ear epithelial cells (HMEECs). TB-conditioned medium (TB-CM) reduced the inflammatory response and regulated mucin and epithelial sodium channel genes in LPS-induced HMEECs...

In proteinuric renal diseases, the serine protease (SP) plasmin activates the epithelial sodium channel (ENaC) by cleaving its γ subunit. We previously demonstrated that a high-salt (HS) diet provoked hypertension and proteinuria in Dahl salt-sensitive (DS) rats, accompanied by γENaC activation, which were attenuated by camostat mesilate (CM), an SP inhibitor. However, the effects of CM on plasmin activity in DS rats remain unclear. In this study, we investigated the effects of CM on plasmin activity, ENaC activation, and podocyte injury in DS rats...

Sodium influx carried out by ion channels is one of the main regulators of water-salt and volume balance in cells of blood origin. Previously, we described amiloride-insensitive ENaC-like channels in human myeloid leukemia K562 cells; the intracellular regulatory mechanisms of the channels are associated with actin cytoskeleton dynamics. Recently, an extracellular mechanism of ENaC-like channels activation in K562 cells by the action of serine protease trypsin has been revealed. The other extracellular pathways that modulate ENaC (epithelial Na+ channel) activity and sodium permeability in transformed blood cells are not yet fully investigated...

BACKGROUND: There is growing consensus that under physiological conditions collecting duct H+ secretion is independent of epithelial sodium channel (ENaC) activity. We have recently shown that the direct ENaC inhibitor benzamil acutely impairs H+ excretion by blocking the renal H+ /K+ -ATPase. However, the question remains whether inhibition of ENaC per se causes alterations in renal H+ excretion. To revisit this question, we studied the effect of the antibiotic trimethoprim (TMP), well known to cause K+ retention by direct ENaC inhibition...

Hypertension is a multifactorial disease characterized by vascular and renal dysfunction, cardiovascular remodeling, inflammation, and fibrosis, all of which are associated with oxidative stress. We previously demonstrated cellular reactive oxygen species (ROS) imbalances may impact the structural and biochemical functions of blood cells and reported downregulation of β-dystroglycan (β-Dg) and overexpression of the epithelial sodium channel (ENaC) contribute to the pathophysiology of hypertension...

PURPOSE OF REVIEW: Hypertension, commonly known as high blood pressure, is a widespread health condition affecting a large number of individuals across the globe. Although lifestyle choices and environmental factors are known to have a significant impact on its development, there is growing recognition of the influence of genetic factors in the pathogenesis of hypertension. This review specifically focuses on the hereditary causes of hypertension that are associated with increased sodium transport through the thiazide-sensitive NaCl cotransporter (NCC) or amiloride-sensitive epithelial sodium channel (ENaC), crucial mechanisms involved in regulating blood pressure in the kidneys...

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined. AIM OF THE STUDY: The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats...

Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single-cell expression and chromatin accessibility tools to characterize the mineralocorticoid target genes and cell types. We demonstrated that mineralocorticoid effects were established through open chromatin and target gene expression, primarily in principal and connecting tubule cells and, to a lesser extent, in segments of the distal convoluted tubule cells. We examined the kidney-protective effects of steroidal and nonsteroidal mineralocorticoid antagonists (MRAs), as well as of amiloride, an epithelial sodium channel inhibitor, in a rat model of deoxycorticosterone acetate, unilateral nephrectomy, and high-salt consumption-induced HTN and cardiorenal damage...

Proteases such as neutrophil elastase cleave and activate the epithelial sodium channel (ENaC), causing airway dehydration. Our current study explores the impact of increased protease levels in vapers' airways on ENaC activity and airway dehydration. Human bronchial epithelial cultures (HBECs) were exposed to bronchoalveolar lavage fluid (BALF) from non-smokers, smokers and vapers. Airway surface liquid (ASL) height was measured by confocal microscopy as a marker of hydration. ENaC cleavage was measured by Western blotting...