Anetoderma: an altered balance between metalloproteinases and tissue inhibitors of metalloproteinases.
The amount of elastic fibers from lesional and healthy skin areas of five patients with anetoderma was determined by automated image analysis. Dermal elastic fibers were almost completely absent in anetodermic skin and preelastic fibers were undetectable or extremely rare. Organ cultures were performed using explants from affected and unaffected skin areas of the same patient. We identified and quantified proteases in the culture media of explants: MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), MMP-7 (matrilysin 1), and tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. The data were compared with those of two healthy donors. For the five samples of anetodermic skin, MMP-1 levels were significantly higher compared with the uninvolved cultures and the two healthy samples. A significant increase of TIMP-1 expression was also observed in the affected cultures. We demonstrated a significant increase in the production of gelatinase A in lesional skin when compared with nonlesional skin and healthy donor samples. We found no significant production of TIMP-2 in the five samples of anetodermic skin compared with the samples from the two healthy donors. There was a significant decrease in TIMP-2 expression in the five nonlesional samples compared with the control samples. These data are in favor of an altered balance in anetodermic patients between MMP-2 and TIMP-2. Levels of MMP-9, MMP-3, and MMP-7 were significantly higher in the culture-conditioned media of the anetodermic skin samples than the nonlesional skin cultures. Because MMP-3, MMP-7, MMP-9 are known to degrade elastin, and MMP-3 can activate the latent forms of MMP-7 and MMP-9, we propose that these metalloproteinases also participate in the degradation of elastic fibers in anetodermic skin.
Ghomrasseni
Sabah
S
Laboratoire de physiopathologie des tissus non minéralisés, Université René Descartes-Paris V, UFR d'Odontologie, 1 Rue Maurice Arnoux, 92120 Montrouge, France.
Dridi
Myriam
M
Gogly
Bruno
B
Bonnefoix
Mireille
M
Vabres
Pierre
P
Venencie
Pierre Yves
PY
Pellat
Bernard
B
Godeau
Gaston
G
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D004547:Elastic Tissue / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012871:Skin Diseases / Q000378:metabolism* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases