Expression of matrix metalloproteinases and their endogenous tissue inhibitors in skin lesions from patients with tuberous sclerosis.
BACKGROUND
Tuberous sclerosis complex lesions of the skin may be disfiguring to patients and can only be treated by laser or cosmetic surgery. Clarification of the molecular and structural changes involved in skin hamartomas may unravel targets for pharmacotherapy.


OBJECTIVE
We investigated the expression of matrix metalloproteinase (MMP) and its tissue inhibitor (TIMP) in fibrous plaques, angiofibromas, and lesion-free skin specimens from patients with tuberous sclerosis complex.


METHODS
Gene expression of MMPs and TIMP-1 was measured by reverse transcription polymerase chain reaction, gelatinase activity by gelatin zymography, and the content of collagenases and TIMPs by enzyme-linked immunosorbent assay.


RESULTS
Compared with lesion-free specimens, hamartomas exhibited decreased levels of TIMPs and messenger RNA expression of TIMP-1, and increased content of MMP-1 and MMP-13 and activity of MMP-9, although gelatinase gene expression was diminished. Gene expression of MMP-15 and MMP-17 was not affected but was diminished for MMP-14.


CONCLUSIONS
The significant variations of the above extracellular matrix molecules between lesion-free specimens and tuberous sclerosis complex hamartomas overall favors a collagenous protein-degrading microenvironment in affected skin, and argue in support of antiprotease treatment for disfiguring skin lesions.
Papakonstantinou
Eleni
E
Department of Pharmacology, Aristotle University of Thessaloniki, Greece.
Dionyssopoulos
Alexander
A
Aletras
Alexios J
AJ
Pesintzaki
Chrisanthi
C
Minas
Aristippos
A
Karakiulakis
George
G
D000328:Adult; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D014020:Tissue Extracts / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery
D061965:Matrix Metalloproteinase Inhibitors; D014020:Tissue Extracts; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1