Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

Schwartz, George J.; Tsuruoka, Shuichi; Vijayakumar, Soundarapandian; Petrovic, Snezana; Mian, A. Mohsin; Al‐Awqati, Qais

doi:10.1172/jci0213292

Cited by 76 publications

(36 citation statements)

References 32 publications

(30 reference statements)

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“…3 Because it has been suggested that ECM hensin and galectin-3 mediate signals that promote acquisition of a terminally differentiated epithelial cell phenotype, 9,10 it would seem that once hensin is deposited in the ECM, a cell could not rapidly de-differentiate. Accordingly, we sought to develop an in vivo model in which we could identify the parameters associated with reversible adaptive changes in intercalated cell phenotypes that define the response of α- and β-intercalated cells to perturbations in acid/base status.…”

Section: Resultsmentioning

confidence: 99%

“…We have examined changes in the physiology of the CCD during metabolic acidosis in vivo 4 and in vitro. 3,5 Indeed, there is an increase in H + secretion and a decrease in

{HCO}_{3}^{-}

secretion in CCDs taken from acidotic rabbits, 4 or after acid incubation. 3,5 In addition, there is a loss of apical anion exchange in β-intercalated cells and a reduction of the apical membrane that binds peanut agglutinin.…”

mentioning

confidence: 97%

“…Intercalated cells, which make up a third of cells of the CCD, 1 are responsible for acid/base transport; α-intercalated cells secrete protons and β-intercalated cells secrete bicarbonate. 2,3 Type α-intercalated cells have apical H + -ATPases and basolateral anion exchangers (AE1), whereas β-intercalated cells express apical anion exchangers (pendrin) and basolateral H + -ATPases. We have examined changes in the physiology of the CCD during metabolic acidosis in vivo 4 and in vitro.…”

mentioning

confidence: 99%

“…3,5 In addition, there is a loss of apical anion exchange in β-intercalated cells and a reduction of the apical membrane that binds peanut agglutinin. 3 …”

mentioning

confidence: 99%

“…Such an acid-induced insertion/activation of basolateral anion exchangers has also been observed by Merot et al 6 We surmised that the change in β-intercalated cell physiology was induced by the deposition of hensin in the ECM underlying these adapting cells. Anti-hensin antibodies, 3 as well as inhibitors of cyclophilin PPIase (peptidylprolyl cis / trans isomerase) activity that block hensin secretion, 7 inhibit acid-induced changes in intercalated cell physiology. 8 Hensin is expressed in many epithelial cells and serves to induce a differentiated phenotype, 9–11 suggesting that differentiation might be difficult to reverse once the matrix is laid down.…”

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confidence: 99%

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Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Purkerson

Tsuruoka

Suter

et al. 2010

Kidney International

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It is well known that acid/base disturbances modulate proton/bicarbonate transport in the cortical collecting duct. To study the adaptation further we measured the effect of three days of acidosis followed by the rapid recovery from this acidosis on the number and type of intercalated cells in the rabbit cortical collecting duct. Immunofluorescence was used to determine the expression of apical pendrin in β-intercalated cells and the basolateral anion exchanger (AE1) in α-intercalated cells. Acidosis resulted in decreased bicarbonate and increased proton secretion, which correlated with reduced pendrin expression and the number of pendrin-positive cells, as well as decreased pendrin mRNA and protein abundance in this nephron segment. There was a concomitant increase of basolateral AE1 and α-cell number. Intercalated cell proliferation did not seem to play a role in the adaptation to acidosis. Alkali loading for 6–20 h after acidosis doubled the bicarbonate secretory flux and reduced proton secretion. Pendrin and AE1 expression patterns returned to control levels, demonstrating that adaptive changes by intercalated cells are rapidly reversible. Thus, regulation of intercalated cell anion exchanger expression and distribution plays a key role in adaptation of the cortical collecting duct to perturbations of acid/base.

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Section: Resultsmentioning

confidence: 99%

“…We have examined changes in the physiology of the CCD during metabolic acidosis in vivo 4 and in vitro. 3,5 Indeed, there is an increase in H + secretion and a decrease in

{HCO}_{3}^{-}

mentioning

confidence: 97%

mentioning

confidence: 99%

“…3,5 In addition, there is a loss of apical anion exchange in β-intercalated cells and a reduction of the apical membrane that binds peanut agglutinin. 3 …”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Purkerson

Tsuruoka

Suter

et al. 2010

Kidney International

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Uriniferous Tubule: Structural and Functional Organization

Christensen

Wagner

Kaissling

2012

Comprehensive Physiology

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The uriniferous tubule is divided into the proximal tubule, the intermediate (thin) tubule, the distal tubule and the collecting duct. The present chapter is based on the chapters by Maunsbach and Christensen on the proximal tubule, and by Kaissling and Kriz on the distal tubule and collecting duct in the 1992 edition of the Handbook of Physiology, Renal Physiology. It describes the fine structure (light and electron microscopy) of the entire mammalian uriniferous tubule, mainly in rats, mice, and rabbits. The structural data are complemented by recent data on the location of the major transport‐ and transport‐regulating proteins, revealed by morphological means (immunohistochemistry, immunofluorescence, and/or mRNA in situ hybridization). The structural differences along the uriniferous tubule strictly coincide with the distribution of the major luminal and basolateral transport proteins and receptors and both together provide the basis for the subdivision of the uriniferous tubule into functional subunits. Data on structural adaptation to defined functional changes in vivo and to genetical alterations of specified proteins involved in transepithelial transport importantly deepen our comprehension of the correlation of structure and function in the kidney, of the role of each segment or cell type in the overall renal function, and our understanding of renal pathophysiology. © 2012 American Physiological Society. Compr Physiol 2:805‐861, 2012.

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Molecular Mechanisms and Regulation of Urinary Acidification

Kurtz

2014

Comprehensive Physiology

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The H+ concentration in human blood is kept within very narrow limits, ~ 40 nM, despite the fact that dietary metabolism generates acid and base loads that are added to the systemic circulation throughout the life of mammals. One of the primary functions of the kidney is to maintain the constancy of systemic acid-base chemistry. The kidney has evolved the capacity to regulate blood acidity by performing three key functions: 1) reabsorb HCO3− that is filtered through the glomeruli to prevent its excretion in the urine; 2) generate a sufficient quantity of new HCO3− to compensate for the loss of HCO3− resulting from dietary metabolic H+ loads and loss of HCO3− in the urea cycle; and 3) excrete HCO3− (or metabolizable organic anions) following a systemic base load. The ability of the kidney to perform these functions requires that various cell types throughout the nephron respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion such that the urine and renal vein chemistry is altered appropriately. The purpose of the article is to provide the interested reader with a broad review of a field that began historically ~ 60 years ago with whole animal studies, and has evolved to where we are currently addressing questions related to kidney acid-base regulation at the single protein structure/function level.

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Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

Cited by 76 publications

References 32 publications

Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Uriniferous Tubule: Structural and Functional Organization

Molecular Mechanisms and Regulation of Urinary Acidification

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