Biomaterial Database

Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts. 1987

S D Clark, and D K Kobayashi, and H G Welgus

Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.

The regulation of the expression of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP) was examined in response to both retinoid compounds and glucocorticoids. Effective retinoids induced a dose-dependent, specific increase in the production of TIMP of approximately two- to threefold by monolayer cultures of human fibroblasts derived from various tissues, while simultaneously causing a decrease in collagenase secretion of similar magnitude. These effects were apparent by 8-12 h in culture and disappeared within 24 h after the withdrawal of retinoid compounds. The retinoid effect on TIMP production was mediated via an increased biosynthesis of new inhibitor protein. Similarly, increased steady state levels of TIMP messenger RNA (mRNA) accompanied by decreased quantities of collagenase mRNA were demonstrated, suggesting transcriptional control of the retinoid action. The data suggest that retinoids co-regulate the expression of collagenase and TIMP, and do so in an inverse manner. Dexamethasone caused a dose-dependent, specific decrease in collagenase production without altering the biosynthesis of TIMP. These findings were paralleled by a marked reduction in collagenase mRNA, without any accompanying change in TIMP mRNA. Therefore, TIMP and collagenase expression appear to be independently modulated by glucocorticoids.

UI	MeSH Term	Description	Entries
D007163	Immunosorbent Techniques	Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.	Immunoadsorbent Techniques,Immunoadsorbent Technics,Immunosorbent Technics,Immunoadsorbent Technic,Immunoadsorbent Technique,Immunosorbent Technic,Immunosorbent Technique,Technic, Immunoadsorbent,Technic, Immunosorbent,Technics, Immunoadsorbent,Technics, Immunosorbent,Technique, Immunoadsorbent,Technique, Immunosorbent,Techniques, Immunoadsorbent,Techniques, Immunosorbent
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008666	Metalloendopeptidases	ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.	Metallo-Endoproteinases,Metalloendopeptidase
D009693	Nucleic Acid Hybridization	Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)	Genomic Hybridization,Acid Hybridization, Nucleic,Acid Hybridizations, Nucleic,Genomic Hybridizations,Hybridization, Genomic,Hybridization, Nucleic Acid,Hybridizations, Genomic,Hybridizations, Nucleic Acid,Nucleic Acid Hybridizations
D011480	Protease Inhibitors	Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).	Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003012	Microbial Collagenase	A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC 3.4.24.3.	Clostridiopeptidase A,Clostridium histolyticum Collagenase,Collagenase, Microbial,Collagenase Clostridium histolyticum,Collagenase-Like Peptidase,Collalysine,Nucleolysin,Clostridium histolyticum, Collagenase,Collagenase Like Peptidase,Collagenase, Clostridium histolyticum,Peptidase, Collagenase-Like,histolyticum, Collagenase Clostridium
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
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