Analysis of the ex vivo specificity of human gelatinases A and B towards skin collagen and elastic fibers by computerized morphometry.
Cutaneous aging and chronic exposure to UV irradiation leads to alterations in the appearance and biochemical composition of the skin. Members of the MMP family have been involved in the destruction of the extracellular matrix. Among them, gelatinases A and B were found to display elastolytic activity, in vitro. In this study, we first determined the ex vivo elastolytic potential of both endopeptidases, using human skin tissue sections and computerized morphometric analyses, and compared it with those of neutrophil elastase. In such conditions, gelatinase B (50 nM) induced 50% elastolysis. The percentage of elastic fibers degraded by gelatinase A (10-100 nM) never exceeded 10%. Elastolysis by gelatinase B and leukocyte elastase was characterized by a decrease in fiber length and an increase in the average diameter of the fibers. In addition, gelatinase B exhibited fibrillin-degrading activities. On the contrary, gelatinase A (50 nM) elicited up to 50% hydrolysis of collagen fibers, preferentially degrading type III collagen fibers. Gelatinase B did not promote any collagen degrading activity. Our data suggested that in vivo gelatinases could disrupt most extracellular matrix structures of human skin. Gelatinase B and to a much lesser extent, gelatinase A would degrade components of the elastic fibers network while gelatinase A, but not gelatinase B, would alter mostly collagen fibers and also degrade constituents of the dermo-epidermal junction.
Berton
A
A
Laboratory of Biochemistry, UPRES-A 6021 CNRS, IFR 53-Biomolecules, Faculty of Medicine, Reims, France.
Godeau
G
G
Emonard
H
H
Baba
K
K
Bellon
P
P
Hornebeck
W
W
Bellon
G
G
D003094:Collagen / Q000378:metabolism*; D004547:Elastic Tissue; D000071837:Fibrillins; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D019272:Leukocyte Elastase / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D018715:Microscopy, Video / Q000379:methods; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013379:Substrate Specificity
D000071837:Fibrillins; D008840:Microfilament Proteins; D003094:Collagen; D019272:Leukocyte Elastase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9