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/jci13292

Cited by 60 publications

(66 citation statements)

References 42 publications

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“…It was previously reported that type B cells might serve as stem cells and give rise to both type A cells and principal cells. 21,22 However, the striking increase in the number of type A cells cannot be explained by conversion of type B IC, because the proportion of type B cells in the OMCD is very low. Moreover, BrdU incorporation was not detected in type B cells.…”

Section: Discussionmentioning

confidence: 99%

Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Song

Kim

Lee

et al. 2007

Journal of the American Society of Nephrology

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Pendrin is an apical anion exchanger found in type B and nonA-nonB intercalated cells that is involved in bicarbonate secretion. The purpose of this study was to establish the origin and fate of pendrinpositive intercalated cells in the mouse kidney. Using immunohistochemistry, we found that pendrinpositive cells first appeared in the connecting tubule at embryonic day 14 (E14) and subsequently in the medullary collecting duct at E18. Most of the pendrin-positive cells in the connecting tubule were nonA-nonB intercalated cells, wheras those in the medullary collecting duct were type B intercalated cells. In the cortical collecting duct, pendrin-positive cells appeared in the inner part at day 4 after birth and in the outer part at day 7. Pendrin-positive cells gradually disappeared by apoptosis from the inner part of the medullary collecting duct two weeks after birth. Using 5-bromo-2Јdeoxy-uridine (BrdU) to follow cell proliferation, we determined that selective proliferation of pendrin-positive intercalated cells does not occur; instead, these cells may arise from undifferentiated precursor cells from separate foci, one in the connecting tubule and one in the collecting duct.

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Section: Discussionmentioning

confidence: 99%

Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Song

Kim

Lee

et al. 2007

Journal of the American Society of Nephrology

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“…Whether altered cell proliferation rates may contribute to the cellular remodeling of the CS epithelium during changes in systemic acid/base homeostasis (Yasoshima et al 1992;Tsuruoka and Schwartz 1996) or during carbonic anhydrase inhibition (Bagnis et al 2001) remains to be analyzed. Some studies (FejesToth and Naray-Fejes-Toth 1992; Yasoshima et al 1992;Schwartz et al 2002) did also suggest that some changes in the prevalence of a particular IC cell subtype might be related to the conversion of one cell type to the other (e.g., from type A IC cells to non-type A IC cells).…”

Section: Discussionmentioning

confidence: 99%

Replication of segment-specific and intercalated cells in the mouse renal collecting system

Wehrli

Loffing‐Cueni

Kaissling

et al. 2006

Histochem Cell Biol

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The renal collecting system (CS) is composed of segment-speciWc (SS) and intercalated (IC) cells. The latter comprise at least two subtypes (type A and non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is unclear. Among other hypotheses, it was proposed that one subtype of IC cells represents a stem cell population from which all cell types in the CS may arise. In the present study, we tested this stem cell hypothesis for the adult kidney by assessing DNA synthesis as a marker for cell replication. SS and IC cells were identiWed by their characteristic expressions of sodium-(epithelial sodium channel, Na-K-ATPase), water-(aquaporin-2) and acid/base-(H + -ATPase, anion exchanger AE1) transporting proteins. Immunostaining for bromodeoxyuridine (BrdU) and for the proliferating cell nuclear antigen (PCNA) was used to reveal DNA synthesis in CS epithelium. BrdU-and PCNA-immunostaining as well as mitotic Wgures were seen in all subtypes of CS cells. Dividing cells retained the cell-type speciWc expression of marker molecules. Treatment of mice with bumetanide combined with a high oral salt intake, which increases the tubular salt load in the CS, profoundly increased the DNA-synthesis rate in SS and non-type A IC cells, but reduced it in type A IC cells.Thus, our data show that DNA synthesis and cell replication occur in each cell lineage of the CS and in diVerentiated cells. The replication rate in each cell type can be diVerently modulated by functional stimulation. Independent proliferation of each cell lineage might contribute to maintain the cellular heterogeneity of the CS of the adult kidney and may also add to the adaptation of the CS to altered functional requirements.

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“…Both pendrin and the putative apical anion exchanger of the type B intercalated cell transport Cl -and HCO 3 -. 8,29 Both apical anion-exchange activity and pendrin protein expression are downregulated in models of metabolic acidosis, eg, with NH 4 Cl ingestion, [12][13][14]30,31 and are upregulated in models of metabolic alkalosis, eg, with NaHCO 3 ingestion. [12][13][14] Apical anion exchange in the CCD is also upregulated by DOCP.…”

Section: Verlander Et Al Mineralocorticoids Upregulate Pendrin In Moumentioning

confidence: 99%

Deoxycorticosterone Upregulates PDS ( Slc26a4 ) in Mouse Kidney

et al. 2003

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Abstract-Pendrin is an anion exchanger expressed along the apical plasma membrane and apical cytoplasmic vesicles of type B and of non-A, non-B intercalated cells of the distal convoluted tubule, connecting tubule, and cortical collecting duct. Thus, Pds (Slc26a4) is a candidate gene for the putative apical anion-exchange process of the type B intercalated cell. Because apical anion exchange-mediated transport is upregulated with deoxycorticosterone pivalate (DOCP), we tested whether Pds mRNA and protein expression in mouse kidney were upregulated after administration of this aldosterone analogue by using quantitative real-time polymerase chain reaction as well as light and electron microscopic immunolocalization. In kidneys from DOCP-treated mice, Pds mRNA increased 60%, whereas pendrin protein expression in the apical plasma membrane increased 2-fold in non-A, non-B intercalated cells and increased 6-fold in type B cells. Because pendrin transports HCO 3 -and Cl -, we tested whether DOCP treatment unmasks abnormalities in acid-base or NaCl balance in Pds (-/-) mice. In the absence of DOCP, arterial pH, systolic blood pressure, and body weight were similar in Pds (ϩ/ϩ) and Pds (-/-) mice. After DOCP treatment, weight gain and hypertension were observed in Pds (ϩ/ϩ) but not in Pds (-/-) mice. Moreover, after DOCP administration, metabolic alkalosis was more severe in Pds (-/-) than Pds (ϩ/ϩ) mice. We conclude that pendrin is upregulated with aldosterone analogues and is critical in the pathogenesis of mineralocorticoid-induced hypertension and metabolic alkalosis.

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

Cited by 60 publications

References 42 publications

Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Replication of segment-specific and intercalated cells in the mouse renal collecting system

Deoxycorticosterone Upregulates PDS ( Slc26a4 ) in Mouse Kidney

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