H+/peptide transporter (PEPT2) is expressed in human epidermal keratinocytes and is involved in skin oligopeptide transport

Abstract

Peptide transporter 2 (PEPT2) is a member of the proton-coupled oligopeptide transporter family, which mediates the cellular uptake of oligopeptides and peptide-like drugs. Although PEPT2 is expressed in many tissues, its expression in epidermal keratinocytes remains unclear. We investigated PEPT2 expression profile and functional activity in keratinocytes. We confirmed PEPT2 mRNA expression in three keratinocyte lines (normal human epidermal keratinocytes (NHEKs), immortalized keratinocytes, and malignant keratinocytes) by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. In contrast to PEPT1, PEPT2 expression in the three keratinocytes was similar or higher than that in HepG2 cells, used as PEPT2-positive cells. Immunolocalization analysis using human skin showed epidermal PEPT2 localization. We studied keratinocyte transport function by measuring the oligopeptide content using liquid chromatography/tandem mass spectrometry. Glycylsarcosine uptake in NHEKs was pH-dependent, suggesting that keratinocytes could absorb small peptides in the presence of an inward H(+) gradient. We also performed a skin-permeability test of several oligopeptides using skin substitute, suggesting that di- and tripeptides pass actively through the epidermis. In conclusion, PEPT2 is expressed in keratinocytes and involved in skin oligopeptide uptake.

Anti-inflammatory effect of collagen tripeptide in atopic dermatitis

“…Interestingly, Kudo et al recently reported that PEPT2 was expressed mainly in keratinocytes. In addition, mRNA levels of PEPTs in fibroblasts were very low in contrast to keratinocytes, and localization of PEPT2 in human skin tissue was not in the dermis but in the epidermis [26]. Supported by this report, CTP may directly affect epidermal keratinocytes via PEPT1 and PEPT2.…”

Potentiating cutaneous wound healing in young and aged skin with nutraceutical collagen peptides

“…It has been suggested that unlike native helical collagen, collagen peptides have specific exposed amino acids that are able to activate cell surface receptors on fibroblasts to directly or indirectly induce their proliferation 14 . Alternatively, collagen peptides may be transported into fibroblasts via proton‐coupled oligopeptide transports, including peptide transporter 2, and peptide histidine transporter (PHT)1 and PHT2, hence further studies are warranted to ascertain the mechanisms by which collagen peptides exert their beneficial effects on cutaneous wound healing 23 …”

Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers

“…PEPT2 is expressed in epidermal keratinocytes [ 48 ]. The maximum concentration of PEPT2 is observed closer to the basal layer of the epidermis.…”