title: Two different cis-acting regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts.
abstract: The expression of the collagen alpha 1(I) gene in activated stellate cells plays an important role during liver fibrogenesis. To identify the critical cis-elements of the collagen alpha 1(I) gene in stellate cells, we used transgenic animals bearing various collagen alpha 1(I) regulatory regions directing the expression of either a human growth hormone minigene or the bacterial beta-galactosidase gene. We found that collagen alpha 1(I)-human growth hormone transgene expression was constitutively high in tendon and skin, provided the transgene contained the -2.3 to -0.44 kb collagen regulatory region. However in the liver, expression was stimulated several-fold, as was the endogeneous gene, by the fibrogenic hepatotoxin carbon tetrachloride. This stimulation occurred whether the collagen 5' regulatory region extended -2.3, -1.6 or -0.44 kb, and in the presence or absence of much of the first intron (+292 to +1607 bp). In addition, the -0.44 kb 5' region was sufficient for high-level transgene expression in stellate cells, following their activation by culture on plastic. In contrast, in skin and tendon, high-level transcription of the collagen alpha 1(I) gene required the -2.3 to -0.44 kb 5' flanking region. Thus, two different cis-regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in stellate cells and in skin and tendon.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, San Diego, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Houglum
authors.forename: M
authors.initials: M
authors.lastname: Buck
authors.forename: J
authors.initials: J
authors.lastname: Alcorn
authors.forename: S
authors.initials: S
authors.lastname: Contreras
authors.forename: P
authors.initials: P
authors.lastname: Bornstein
authors.forename: M
authors.initials: M
authors.lastname: Chojkier
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012867:Skin / Q000378:metabolism*; D013710:Tendons / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D003094:Collagen