Biomaterial Database

TNF-alpha inhibits liver collagen-alpha 1(I) gene expression through a tissue-specific regulatory region. 1998

K Houglum, and M Buck, and D J Kim, and M Chojkier

Department of Medicine, Veterans Affairs Medical Center, San Diego, California, USA.

Although tumor necrosis factor-alpha (TNF-alpha) inhibits collagen-alpha 1(I) gene expression in cultured hepatic stellate cells, assessment of its effects on hepatic collagen expression is complicated by the confounding variables of tissue necrosis and inflammation. Therefore, we analyzed whether chronically elevated serum TNF-alpha affects constitutive hepatic collagen metabolism in vivo by inoculating nude mice with Chinese hamster ovary (CHO) cells secreting TNF-alpha (TNF-alpha mice) or with control CHO cells (control mice). Before the onset of weight loss, collagen synthesis and collagen gene expression were inhibited in the liver of TNF-alpha mice. In transgenic mice, after 8 h, TNF-alpha (500 ng at 0 and 5 h) inhibited the liver expression of the collagen-alpha 1(I)-human growth hormone (hGH) transgene containing the first intron and -440 bp of the 5' region. Similarly, in cultured hepatic stellate cells isolated from these transgenic animals, the -440 bp collagen-alpha 1(I)-hGH transgene was responsive to TNF-alpha treatment independent of the activation of these cells. Transfection studies in stellate cells allowed further characterization of this TNF-alpha-responsive segment to -220 bp of the 5' region. Because in the skin the inhibitory effect of TNF-alpha involves a regulatory region of the collagen-alpha 1(I) gene beyond -440 bp, we herein identify a novel tissue-specific regulation of collagen-alpha 1(I) gene by TNF-alpha.

UI	MeSH Term	Description	Entries
D007536	Isomerism	The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Isomerisms
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008819	Mice, Nude	Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.	Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D003094	Collagen	A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).	Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man