Abstract

The dermal-epidermal junction (DEJ) provides a physical and biological interface between the epidermis and the dermis. In addition to providing a structural integrity, the DEJ also acts as a passageway for molecular transport. Based on the recently reported importance of the DEJ in skin aging, novel peptide derivatives have been tested for their effects on basement membrane (BM) protein expressions in cultured human epidermal keratinocytes. As a result, protein expressions of collagen XVII, laminin and nidogen were stimulated by the test peptide and peptides complex. Further ex vivo evaluation using excised human skin, confirmed that the topical application of the peptides complex significantly increased dermal collagen expression, as well as expressions of collagen XVII and laminin. Interestingly, while the origin of the laminin protein is epidermal keratinocytes, the immunohistochemical staining of skin showed that laminin was only detected in the uppermost layer of the dermis, which suggests a tight assembly of laminin protein onto the dermal side of the DEJ. These results suggest that a peptide complex could improve the structural properties of the DEJ through its ability to stimulate BM proteins. In order to evaluate the anti-wrinkle benefits of the peptide complex in vivo, a clinical study was performed on 22 healthy Asian female volunteers older than 40 years. As a result, significant improvements in skin wrinkles for all of the five sites were observed after two weeks, as assessed by skin topographic measurements. Collectively, these results demonstrate the anti-aging efficacy of the peptides complex.

Highlights

  • The dermal-epidermal junction (DEJ) separates the epidermal and dermal compartments of the skin, and provides a biochemical interface between the epidermis and the dermis

  • This impairment results from elevated expressions of extracellular matrix degrading enzymes, including matrix metalloproteinases (MMPs), urinary plasminogen-activator/plasmin and heparinase, which can degrade the epidermal basement membrane (BM) comprising proteins [3]

  • As a derivative of the growth hormone-releasing peptide (GHRP), we recently reported that biotin-conjugated GHRP-6 peptide induced collagen and insulin-like growth factor-1 (IGF-1) expressions in cultured human myoblasts [16], which suggests a potential application for topical usage

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Summary

Introduction

The dermal-epidermal junction (DEJ) separates the epidermal and dermal compartments of the skin, and provides a biochemical interface between the epidermis and the dermis. While a similar change was observed for photoaged skin, additional structural impairment, expressed as a disrupted and multilayered lamina densa under an electron microscope, is reported [2] This impairment results from elevated expressions of extracellular matrix degrading enzymes, including matrix metalloproteinases (MMPs), urinary plasminogen-activator (uPA)/plasmin and heparinase, which can degrade the epidermal basement membrane (BM) comprising proteins [3]. These structural changes and consequent diminution of molecular exchanges between the epidermis and the dermis result in various age-related changes, such as an impairment of epidermal permeability barrier functions [4], decreased wound healing [5] and skin dryness [6]

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