Importance of balance between extracellular matrix synthesis and degradation in basement membrane formation.
The epidermal basement membrane (BM) plays important roles in adhesion between epidermis and dermis and in controlling epidermal differentiation. In a skin-equivalent (SE), components of the epidermal BM such as laminin 5 and type IV and VII collagens were detected in conditioned media and in basal keratinocytes. Despite production of these BM components, however, BM was rarely observed at the dermal-epidermal junction. One possible explanation for the absence of BM in SEs is that matrix metalloproteinases (MMPs) degrade newly synthesized extracellular matrices. In fact, several MMPs, such as MMPs-1, 2, 3, and 9, were observed to be present in conditioned media and some of them were in active forms. Tissue inhibitor of metalloproteinase (TIMP)-2 was not detected, although TIMP-1 was present. BM degradation activity presumably exceeds BM formation activity in the SE, resulting in the absence of lamina densa at the dermal-epidermal junction. Synthetic MMP inhibitors CGS27023A and MMP inhibitor I, which inhibit MMPs 1, 2, 3, and 9, markedly augmented deposition of laminin 5 and type IV and VII collagens at the dermal-epidermal junction, resulting in formation of continuous epidermal BM. These results suggest that the balance between synthesis and degradation of BM components is important for BM formation.
Amano
S
S
Shiseido Life Science Research Center, Yokohama, 236-8643, Japan. satoshi.amano@to.shiseido.co.jp
Akutsu
N
N
Matsunaga
Y
Y
Nishiyama
T
T
Champliaud
M F
MF
Burgeson
R E
RE
Adachi
E
E
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D024141:Collagen Type IV / Q000187:drug effects / Q000378:metabolism; D024143:Collagen Type VII / Q000187:drug effects / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007797:Laminin / Q000187:drug effects / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D024141:Collagen Type IV; D024143:Collagen Type VII; D004791:Enzyme Inhibitors; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; C097043:laminin alpha5; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9