Biomaterial Database

Integrin alpha2beta1-dependent contraction of floating collagen gels and induction of collagenase are inhibited by tyrosine kinase inhibitors. 1996

A Broberg, and J Heino

MediCity Research Laboratory and Department of Medical Biochemistry, University of Turku, Finland.

A cell culture inside a three-dimensional gel of fibrillar collagen is an experimental model used to study the response of cells to the extracellular matrix. Many cell types induce the contraction of gel and simultaneously decrease their production of type I collagen, whereas the expression of interstitial collagenase (matrix metalloproteinase-1; MMP-1) is enhanced. We have previously shown that in osteogenic cells the collagen receptor alpha2beta1 integrin is a positive regulator of MMP-1 and that the number of alpha2beta1 integrins on the cell surface also regulates the magnitude of contraction. However, the downregulation of collagen mRNA levels is not initiated by alpha2beta1 integrin. Here, we have studied in human KHOS-240 and MG-63 osteosarcoma cells and in human skin fibroblasts the effects of tyrosine kinase inhibitors on collagen gel contraction and on the regulation of MMP-1 and collagen alpha1(I) genes by extracellular collagen. The induction of MMP-1 could be inhibited by all tyrosine kinase inhibitors tested with the exception of genistein. None of them could prevent the downregulation of collagen expression. Thus, the collagen-induced alterations in the expression of MMP-1 and collagen alpha1(I) seem to be dependent on distinct signal transduction pathways. Many of the inhibitors, including genistein, could prevent the contraction of collagen gels. The effect was not related to their ability to inhibit cell growth, because an inhibitor specific for DNA synthesis and cell division did not have the same effect. Thus, we suggest that the process of collagen gel contraction requires protein-tyrosine phosphorylation and that the ability of cells to contract collagen gels is not related to the induction of MMP-1 or to the level of collagen alpha1(I) expression. Finally, we propose that the tyrosine kinase inhibitors might be considered as candidate molecules in the treatment of pathological scar contraction.

UI	MeSH Term	Description	Entries
D007529	Isoflavones	3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.	3-Benzylchroman-4-One,3-Benzylidene-4-Chromanone,Homoisoflavone,Homoisoflavones,Isoflavone,Isoflavone Derivative,3-Benzylchroman-4-Ones,3-Benzylidene-4-Chromanones,Isoflavone Derivatives,3 Benzylchroman 4 One,3 Benzylchroman 4 Ones,3 Benzylidene 4 Chromanone,3 Benzylidene 4 Chromanones,Derivative, Isoflavone,Derivatives, Isoflavone
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002109	Caffeic Acids	A class of phenolic acids related to chlorogenic acid, p-coumaric acid, vanillic acid, etc., which are found in plant tissues. It is involved in plant growth regulation.	Acids, Caffeic
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
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
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005109	Extracellular Matrix	A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.	Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D005782	Gels	Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.