Microbiome-Supporting BM Skin Care
A recent study compared the effect of microbiome-supporting skin care with conventional products on skin microbiome and biophysical parameters. The results showed that BM skin care significantly improved the skin’s structure and texture.
The basement membrane (BM) is a connecting protein complex that provides physical and molecular adherence to the epidermis and dermis. Among the BM components are collagen IV, laminin and nidogen.
Collagen XVII
Collagen XVII is an important component of hemidesmosomes, microscopic structures that anchor the epidermis to the underlying skin. These structures are largely responsible for the mechanical strength of the skin. In addition, hemidesmosomes provide an extracellular matrix that supports the proliferation of epidermis stem cells and regulates epidermal homeostasis. This study has revealed that the absence of collagen XVII leads to transient epidermal hyperproliferation in a mouse model, and that overexpression of this protein suppresses this proliferation. This work also provides evidence that hematidesmosomal collagen XVII interacts with the Wnt signaling pathway to control cell growth in the epidermis.
The COL17A1 gene provides instructions for making the alpha chain of type XVII collagen. This protein is a structural component of hemidesmosomes, multiprotein complexes in the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying epidermis. Mutations in this gene are associated with the autoimmune blistering diseases bullous pemphigoid and junctional epidermolysis bullosa. Two homotrimeric forms of this protein exist, a 180-kDa full length transmembrane form and a 120-kDa soluble form generated by proteolytic processing.
We studied the reactivity of autoantibodies against the 180-kDa hemidesmosomal collagen XVII in aesthetic skin care sera from patients with bullous pemphigoid (BP), cicatricial epidermolysis bullosa (CEB), and linear IgA dermatosis (LAD). All circulating autoantibodies against this protein bound to the soluble 120-kDa hemidesmosomal ectodomain. We observed that the ectodomain contains both neoepitopes and cross-reactive epitopes against a variety of epidermal basement membrane proteins, suggesting that the soluble form of this protein can act as a bridge between the intracellular and extracellular domains.
Laminin
Laminins are a class of proteins that form the structural components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. They are critical for maintaining the integrity of basement membranes in skin and other organ systems and promote cell adhesion. They are also important for regulating the growth and migration of cells, as well as forming and organizing basement membranes in specialized cellular structures such as hair follicles and blood vessels.
The epidermal basement membrane is a specialized zone of the extracellular matrix (ECM) that divides the skin into two major parts, the epidermis and the dermis. The epidermal-dermal junction (DEJ) is a critical site of communication between these two compartments and plays a key role in the maintenance of homeostasis of the skin. The DEJ is composed of specific structures including the basement membrane (BM) and epidermal keratinocytes.
In addition, the BM is also made up of specific components that provide physical adherence between the epidermis and dermis, including nidogens and collagen IV. A decrease in the expression of these proteins has been associated with aging of the skin and may contribute to wrinkle formation.
Among the several different isoforms of laminin in mammals, laminin-332 and 511 are major constituents of the BM that aesthetic skin care shop separates the epidermis from the dermis. They are also enriched in the epidermal keratinocyte cytoplasm and play a critical role in the anchoring complex for the epidermis to the BM. Mice lacking the a3-b3-g2 subunits of laminin-332 die at a very early age from blistering, suggesting that the defect in this isoform impairs epidermal-BM interaction. This is consistent with the phenotype of patients afflicted with herlitz junctional epidermolysis bullosa (HJEB), which is caused by mutations in genes that encode for laminin-332 subunits (33).
Nidogen
Nidogen, along with laminins and collagen IV, forms the bridging glycoprotein component of the basement membrane (BM). Nidogen-1 has been shown to act as a high-affinity binding protein for both collagen IV and perlecan, suggesting that it is critical to BM assembly. In vivo, loss of nidogen in Caenorhabditis elegans results in aberrant axonal migration but does not affect morphologically normal BMs. In contrast, mouse nidogen gene knockout results in BM defects and skeletal abnormalities. Nidogen-1 has also been shown to cooperate with laminin-1 in stimulating b-casein synthesis by cultured mammary epithelial cells.
The crystal structure of nidogen-1 G2 in complex with perlecan IG3 reveals that the N-terminal epidermal growth factor-like domain forms a central F-G turn, which provides three metal ligands to perlecan and is in van der Waals contact with an E-F turn of the adjacent IG3 domain. The crystallographic data suggest that the nidogen-perlecan interaction is mediated by a salt bridge and a disulfide bond. The nidogen-perlecan complex also contains an unusually large pore, which is likely to be important for membrane trafficking.
In vivo, nidogen is present pericellularly in adipocytes, endothelial cells, chondrocytes, fibroblasts, and nerve cells of the musculoskeletal system in a laminar arrangement and plays an essential role in lineage differentiation. In humans, two nidogen isoforms have been identified: nidogen-1 and nidogen-2.
Biotinylated peptides
The dermal-epidermal junction (DEJ) is an important interface between the epidermis and the dermis. It is a passageway for molecular transport and provides structural integrity to the skin. This research focuses on the identification of peptides as potential cosmeceutical ingredients for anti-aging products that target the DEJ by stimulating the expression of the proteins involved in this process.
The synthesis of biotinylated peptides has been a common approach for developing new cosmetic ingredients. The peptides are linked to biotin by the synthesis of a dimeric enzyme, N- or C-terminal biotinylation, and by the use of different spacers. This allows for the selective enrichment of a specific peptide from complex mixtures, and can be used for proteomics studies or pull down experiments.
These peptides are often conjugated to vitamin C, which enhances their activity. In the present study, a combination of biotinylated hexapeptide and a hexapeptide derived from histone H3.1 was tested for its ability to stimulate the expression of BM proteins in cultured human epidermal keratinocytes. Treatment of cells with the peptides resulted in significant increases in laminin and nidogen protein expression. In addition, a topical application of the peptides complex significantly increased the expression of these proteins in ex vivo excised human skin.
While many cosmeceutical companies develop new peptide sequences with beneficial effects, peptides that are already known to have beneficial properties are increasingly being used. Especially the application of peptides as a replacement for synthetic molecules is very attractive, because the natural biological active compounds have many advantages over synthetic chemicals. These include their favourable safety profile and the low production costs.
