Title:Heparanase Inhibitors Facilitate the Assembly of the Basement Membrane in Artificial Skin
Volume: 5
Issue: 2
Author(s): Makoto Tsunenaga
Affiliation:
Keywords:
Basement membrane, heparan sulfate, heparanase, inhibitor, matrix metalloproteinase, three-dimensional culture.
Abstract: Recent research suggests that the basement membrane at the dermalepidermal
junction of the skin plays an important role in maintaining a healthy epidermis
and dermis, and repeated damage to the skin can destabilize the skin and accelerate
the aging process. Skin-equivalent models are suitable for studying the reconstruction
of the basement membrane and its contribution to epidermal homeostasis
because they lack the basement membrane and show abnormal expression of
epidermal differentiation markers. By using these models, it has been shown that reconstruction
of the basement membrane is enhanced not only by supplying basement
membrane components, but also by inhibiting proteinases such as urokinase
and matrix metalloproteinase. Although matrix metalloproteinase inhibitors assist in
the reconstruction of the basement membrane structure, their action is not sufficient to promote its functional
recovery. However, heparanase inhibitors stabilize the heparan sulfate chains of perlecan (a
heparan sulfate proteoglycan) and promote the regulation of heparan sulfate binding growth factors in
the basement membrane. Heparan sulfate promotes effective protein-protein interactions, thereby facilitating
the assembly of type VII collagen anchoring fibrils and elastin-associated microfibrils. Using
both matrix metalloproteinase inhibitors and heparanase inhibitors, the basement membrane in a skinequivalent
model comes close to recapitulating the structure and function of an in vivo basement membrane.
Therefore, by using an appropriate dermis model and suitable protease inhibitors, it may be possible
to produce skin-equivalent models that are more similar to natural skin.
