Expression of transcription factors in keratoconus, a cornea-thinning disease.
Transcription factors are known to regulate gene transcription through the recognition and binding of specific DNA sequences in the promoter or enhancer regions of many genes. Keratoconus is a cornea-thinning disease in which upregulated expression of degradative enzymes and downregulated expression of protease inhibitors have been demonstrated. In view of the alteration in gene expression for multiple proteins, five common transcription factors, AP1, AP2, CREB, Sp1, and NF-kappa B were examined for their possible roles in keratoconus. Immunostaining experiments and Western blotting showed that Sp1 exhibited enhanced expression in keratoconus corneas. Increased binding of Sp1 consensus sequence oligonucleotides with nuclear extracts from the epithelium of keratoconus corneas was also seen by gel mobility shift assays. This is believed to be a first demonstration connecting Sp1 alteration to a human disease. The elevated Sp1 expression may contribute to the enzyme and inhibitor abnormalities found in keratoconus corneas.
Whitelock
R B
RB
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, 60612, USA.
Li
Y
Y
Zhou
L L
LL
Sugar
J
J
Yue
B Y
BY
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007640:Keratoconus / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors