title: Importance of balance between extracellular matrix synthesis and degradation in basement membrane formation.
abstract: 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.
authors.affiliation: Shiseido Life Science Research Center, Yokohama, 236-8643, Japan. satoshi.amano@to.shiseido.co.jp
authors.forename: S
authors.initials: S
authors.lastname: Amano
authors.forename: N
authors.initials: N
authors.lastname: Akutsu
authors.forename: Y
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: T
authors.initials: T
authors.lastname: Nishiyama
authors.forename: M F
authors.initials: MF
authors.lastname: Champliaud
authors.forename: R E
authors.initials: RE
authors.lastname: Burgeson
authors.forename: E
authors.initials: E
authors.lastname: Adachi
mesh_terms: 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
chemical_list: 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