This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0030OCv1 29/4/499    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Holmes, K. W. Articles by Zeitlin, P. L. Search for Related Content PubMed PubMed Citation Articles by Holmes, K. W. Articles by Zeitlin, P. L.

Modulation of Sp1 and Sp3 in Lung Epithelial Cells Regulates ClC-2 Chloride Channel Expression

Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Address correspondence to: Dr. Pamela L. Zeitlin, Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, 600 N Wolfe St. Park 316, Baltimore, MD 21287–2533. E-mail: pzeitlin{at}jhmi.edu

ClC-2 is a pH- and voltage-activated chloride channel, which is highly expressed in fetal airways and downregulated at birth. The ClC-2 promoter contains consensus binding sites within the first 237 bp, which bind transcription factors Sp1 and Sp3(1). This study directly links Sp1 and Sp3 with ClC-2 protein expression by demonstrating: (i) induction of ClC-2 protein by transient overexpression of each transcription factor in adult rat Type II cells, which have low levels of ClC-2; and (ii) reduction of ClC-2 expression by incubation with a competitive inhibitor of Sp1 and Sp3 in fetal rat Type II cells, which have high levels of endogenous ClC-2. Endogenous fetal lung Sp1 is differentially expressed as two major species of 105 kD and 95 kD. Although low-level expression of Sp1 in adult cells is almost exclusively the 105-kD species, overexpression of Sp1 results in increased expression of the 95-kD band. These experiments suggest that the mechanism for postnatal reduction of ClC-2 expression in lung epithelia is based on decreased interaction of Sp1 and Sp3 with the ClC-2 promoter.

Abbreviations: bovine serum albumin, BSA • cystic fibrosis, CF • CF transmembrane conductance regulator, CFTR • Dulbecco's phosphate-buffered saline with calcium and magnesium, DPBS • sodium dodecyl sulfate–polyacrylamide gel electrophoresis, SDS-PAGE

This article has been cited by other articles:

				N. Vij and P. L. Zeitlin Regulation of the ClC-2 Lung Epithelial Chloride Channel by Glycosylation of SP1 Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 754 - 759. [Abstract] [Full Text] [PDF]