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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 1, July, 2001 119-124

Cloning of Dexamethasone-Induced Transcript
A Novel Glucocorticoid-Induced Gene that Is Upregulated in Emphysema

Alasdair J. Edgar, Emma J. Birks, Magdi H. Yacoub, and Julia M. Polak

Department of Histochemistry, Division of Investigative Sciences, Imperial College School of Medicine, London; and Imperial College School of Medicine at the Heart Science Centre, Harefield Hospital, Harefield, Middlesex, United Kingdom

To identify changes in gene expression associated with emphysema, we used differential display to compare RNA extracted from emphysematous lungs with that of unused donor tissues taken at the time of transplant. A differentially expressed sequence was identified corresponding to the 3' end of a novel human complementary DNA (cDNA) of unknown function. The human and mouse cDNA sequences were completed by 5' rapid amplification of cDNA ends. We have named it DEXI for dexamethasone-induced transcript. DEXI messenger RNA (mRNA) was upregulated 147% in emphysematous tissue compared with donor tissue. DEXI mRNA was also upregulated 230% by dexamethasone treatment of A549. The increase in expression of DEXI found in emphysema patients' tissues may be owing to their known treatment with corticosteroids. The human DEXI gene is intronless and the predicted open reading frame encodes a 95-residue acidic protein. Database searches revealed the presence of homologues only in mammals, and a human pseudogene. The protein has a predicted central transmembrane domain and a carboxy-terminal leucine zipper. The human mRNA has a single 1.3-kb transcript. We suggest that the increased expression of DEXI in emphysema may either be relevant to disease progression or be indicative of glucocorticoid responsiveness in treated patients.

Abbreviations: alpha 1-antitrypsin, alpha 1-AT; base pair(s); bp; complementary DNA, cDNA; chronic obstructive pulmonary disease, COPD; carboxy terminal, CT; dexamethasone-induced transcript, DEXI; expressed sequence tag, EST; glyceraldehyde-3-phosphate dehydrogenase, G3PDH; messenger RNA, mRNA; open reading frame, ORF; polymerase chain reaction, PCR; rapid amplification of cDNA ends, RACE; reverse transcriptase, RT; untranslated region, UTR.






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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
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