Referenced in: none

Automatically associated channels: ClC2 , ClC4 , Kir6.2

Title: Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression.

Authors: Kathryn W Holmes, Russell Hales, Shijian Chu, Micah J Maxwell, Peter J Mogayzel, Pamela L Zeitlin

Journal, date & volume: Am. J. Respir. Cell Mol. Biol., 2003 Oct , 29, 499-505

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12714379

Abstract
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.