Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts. 1995

M Kiss, and M Wlaschek, and P Brenneisen, and G Michel, and C Hommel, and T S Lange, and D Peus, and L Kemeny, and A Dobozy, and K Scharffetter-Kochanek
Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.

Recent reports have suggested that alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in untraviolet (UV) irradiation mediated skin changes including pigmentation, inflammation and connective tissue damage. alpha-MSH synthesis has been found to be induced in human keratinocytes following UV irradiation. In order to test the hypothesis whether UV induced alpha-MSH - via a paracrine loop - regulates the synthesis and the activity of collagenase/MMP-1, we studied the effects of alpha-MSH on the expression of MMP-1 and its tissue inhibitor of matrix metalloproteinases (TIMP-1). Confluent human dermal fibroblast cultures from foreskin biopsies of healthy human donors were treated with 10(-5)M, 10(-8)M and 10(-11)M alpha-MSH for 30 min. As determined by Northern blot analysis 10(-5)M and 10(-8)M alpha-MSH dose- and time-dependently induced steady state levels of MMP-1 mRNA up to 9-fold compared to untreated controls. TIMP-1 mRNA steady state levels were also slightly induced, however, the increased MMP-1/TIMP-1 ratio when normalized to beta-actin reflected an unbalanced synthesis. MMP-1 protein expression was studied with an immunofluorescence technique using a monoclonal antibody against MMP-1. After alpha-MSH treatment an increased number of fibroblasts revealed an intense perinuclear staining pattern compared to the less intense staining of control fibroblasts. The overall collagenolytic activity of supernatants from alpha-MSH treated fibroblasts was increased by 35%. Our data support the view that UV induced alpha-MSH - by the stimulation of collagenase/MMP-1 - may contribute to the loss of interstitial collagen related to cutaneous photoaging.

UI MeSH Term Description Entries
D002457 Cell Extracts Preparations of cell constituents or subcellular materials, isolates, or substances. Cell Extract,Extract, Cell,Extracts, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
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
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000521 alpha-MSH A 13-amino acid peptide derived from proteolytic cleavage of ADRENOCORTICOTROPIC HORMONE, the N-terminal segment of ACTH. ACTH (1-13) is amidated at the C-terminal to form ACTH (1-13)NH2 which in turn is acetylated to form alpha-MSH in the secretory granules. Alpha-MSH stimulates the synthesis and distribution of MELANIN in MELANOCYTES in mammals and MELANOPHORES in lower vertebrates. MSH, alpha,alpha Intermedin,alpha-Melanocyte-Stimulating Hormone,(Des-Acetyl)-alpha-MSH,(Desacetyl)alpha-MSH,ACTH (1-13),ACTH (1-13)NH2,ACTH(1-13),Acetylated ACTH (1-13)NH2,Adrenocorticotropin (1-13)NH2,DE-alpha-MSH,Des-Acetyl MSH,Desacetyl alpha-MSH,Desacetyl alpha-Melanocyte-Stimulating Hormone,MSH, (Desacetyl)alpha-,alpha-Melanotropin,Desacetyl alpha MSH,Desacetyl alpha Melanocyte Stimulating Hormone,Hormone, Desacetyl alpha-Melanocyte-Stimulating,Hormone, alpha-Melanocyte-Stimulating,Intermedin, alpha,MSH, Des-Acetyl,alpha MSH,alpha Melanocyte Stimulating Hormone,alpha Melanotropin,alpha-MSH, Desacetyl,alpha-Melanocyte-Stimulating Hormone, Desacetyl

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