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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/C1261    most recent 00486.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Adler, L. Articles by Zelikovic, I. Search for Related Content PubMed PubMed Citation Articles by Adler, L. Articles by Zelikovic, I.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Molecular mechanisms of epithelial cell-specific expression and regulation of the human anion exchanger (pendrin) gene

¹Laboratory of Developmental Nephrology, Department of Physiology and Biophysics, Faculty of Medicine and ²The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology; and ³Pediatric Nephrology Unit, Rambam Medical Center, Haifa, Israel

Submitted 16 October 2007 ; accepted in final form 27 February 2008

Pendrin, a Cl^–/anion exchanger encoded by the gene PDS, is highly expressed in the kidney, thyroid, and inner ear epithelia and is essential for bicarbonate secretion, iodide accumulation, and endolymph ion balance, respectively. This study aimed to define promoter regulatory elements essential for renal, thyroid, and inner ear epithelial cell-specific expression of human PDS (hPDS) and to explore the effect of ambient pH and aldosterone on hPDS promoter activity. Endogenous pendrin mRNA and protein were detected in renal HEK293, thyroid LA2, and inner ear VOT36 epithelial cell lines, but not in the fibroblast cell line, NIH3T3. A 4.2-kb hPDS 5'-flanking DNA sequence and consecutive 5'-deletion products were cloned into luciferase reporter vectors and transiently transfected into the above cell lines. Distinct differences in expression/activity of deduced positive/negative regulatory elements within the hPDS promoter between HEK293, LA2, and VOT36 cells were demonstrated, with only basal activity in NIH3T3 cells. Acidic pH (7.0–7.1) decreased and alkaline pH (7.6–7.7) increased hPDS promoter activity in transfected HEK293 and VOT36, but not in LA2 cells. Aldosterone (10^–8 M) reduced hPDS promoter activity in HEK293 but had no effect in LA2 and VOT36 cells. These pH and aldosterone-induced effects on the hPDS promoter occurred within 96-bp and 89-bp regions, respectively, which likely contain distinct response elements to these modulators. Acidic pH and aldosterone decreased, and alkaline pH increased, endogenous pendrin mRNA level in HEK293 cells. In conclusion, pendrin-mediated HCO₃^– secretion in the renal tubule and anion transport in the endolymph may be regulated transcriptionally by systemic pH and aldosterone.

acid-base transport; aldosterone; kidney; thyroid; inner ear

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