Opening lines of communication in the distal nephron

Kleyman, Thomas R.; Satlin, Lisa M.; Hallows, Kenneth R.

doi:10.1172/jci71944

Cited by 15 publications

(12 citation statements)

References 20 publications

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“…The observations that the mechanism of NaCl absorption in the endolymphatic sac has some similarity to that in intercalated cells of the renal collecting duct is not surprising since both cell populations are members of the FORE family ( Hulander et al, 2003 ; Vidarsson et al, 2009 ). The renal collecting duct epithelia consist of at least three cell types, α intercalated cells, β intercalated cells, and principal cells ( Kleyman et al, 2013 ). The α intercalated cells are mainly responsible for urinary acidification through v-ATPase on the apical membrane and anion exchanger 1 SLC4A1 (AE1) on the basolateral membrane.…”

Section: Discussionmentioning

confidence: 99%

Molecular architecture underlying fluid absorption by the developing inner ear

Honda

Kim

Kelly

et al. 2017

eLife

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Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and S3226. Single-cell RNA-seq analysis of pre- and postnatal endolymphatic sacs demonstrates two types of differentiated cells. Early ribosome-rich cells (RRCs) have a transcriptomic signature suggesting expression and secretion of extracellular proteins, while mature RRCs express genes implicated in innate immunity. The transcriptomic signature of mitochondria-rich cells (MRCs) indicates that they mediate vectorial ion transport. We propose a molecular mechanism for resorption of NaCl by MRCs during development, and conclude that disruption of this mechanism is the root cause of hearing loss associated with EES.

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Section: Discussionmentioning

confidence: 99%

Molecular architecture underlying fluid absorption by the developing inner ear

Honda

Kim

Kelly

et al. 2017

eLife

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“…ENaC is primarily expressed in the apical membrane of late distal tubule epithelial cells, which is also known as the ASDN. In addition to its role in Na + reabsorption, ENaC also plays a critical role in the secretion of K + in the ASDN [31,74,75]. The discovery of mutations in the human ENaC channel confirmed the role of ENaC in regulating blood pressure homeostasis.…”

Section: Enac Function In the Kidneymentioning

confidence: 90%

ENaC in Salt-Sensitive Hypertension: Kidney and Beyond

et al. 2020

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Purpose of Review The main goal of this article is to discuss the role of the epithelial sodium channel (ENaC) in extracellular fluid and blood pressure regulation. Recent Findings Besides its role in sodium handling in the kidney, recent studies have found that ENaC expressed in other cells including immune cells can influence blood pressure via extra-renal mechanisms. Dendritic cells (DCs) are activated and contribute to salt-sensitive hypertension in an ENaC-dependent manner. We discuss recent studies on how ENaC is regulated in both the kidney and other sites including the vascular smooth muscles, endothelial cells, and immune cells. We also discuss how this extra-renal ENaC can play a role in salt-sensitive hypertension and its promise as a novel therapeutic target. Summary The role of ENaC in blood pressure regulation in the kidney has been well studied. Recent human gene sequencing efforts have identified thousands of variants among the genes encoding ENaC, and research efforts to determine if these variants and their expression in extra-renal tissue play a role in hypertension will advance our understanding of the pathogenesis of ENaCmediated cardiovascular disease and lead to novel therapeutic targets.

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“…The question remains of how these two disparate cell types coordinate their function in these epithelia (20,34). The plasma membrane of each epithelial cell organizes into apical and basolateral domains that develop distinct membrane lipid and transport protein compositions.…”

Section: Intercalated Cell Distribution Nomenclature Morphology Anmentioning

confidence: 99%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

204

213

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Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.

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Opening lines of communication in the distal nephron

Cited by 15 publications

References 20 publications

Molecular architecture underlying fluid absorption by the developing inner ear

Molecular architecture underlying fluid absorption by the developing inner ear

ENaC in Salt-Sensitive Hypertension: Kidney and Beyond

Collecting Duct Intercalated Cell Function and Regulation

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