Importance of Balance between Extracellular Matrix Synthesis and Degradation in Basement Membrane Formation |
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Authors: | Satoshi Amano Nobuko Akutsu Yukiko Matsunaga Kuniko Kadoya Toshio Nishiyama Marie-France Champliaud Robert E Burgeson Eijiro Adachi |
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Institution: | Shiseido Life Science Research Center, Yokohama, 236-8643, Japan. satoshi.amano@to.shiseido.co.jp |
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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. |
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Keywords: | laminin 5 type IV collagen type VII collagen basement membrane MMPs |
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