title: Effect of prolactin-induced protein on human skin: new insight into the digestive action of this aspartic peptidase on the stratum corneum and its induction of keratinocyte proliferation.
abstract: Human prolactin-induced protein (PIP) is a major protein found in exocrine fluids such as saliva and sweat. Intriguingly, PIP possesses residues (human PIP (hPIP): PIP (29-63)) that display similarity to the aspartic peptidase candidapepsin. Here, we aimed to determine the effect of PIP as a protease on normal skin structure. Using an adhesive tape-stripping technique, we applied hPIP peptide on the corneocytes of normal-appearing facial skin from infants with eczema and healthy infants and then analyzed the morphological structure of corneocytes with Nile Red fluorescence. We also repeatedly applied the hPIP peptide onto the surface of a three-dimensional (3-D) human skin model and then analyzed any changes to the stratum corneum and epidermis using light microscopy and scanning electron microscopy. In both infant groups, a decrease in hydrophobic lipids from the cornified envelope was observed after treatment with hPIP. The peptide hPIP appeared to digest the fine structure of the stratum corneum and induce a proliferation of epidermal keratinocytes within the 3-D human skin model. Our results suggest that aspartic peptidase of PIP found in sweat or saliva deteriorates the skin barrier in a de novo manner, which potentially leads directly to the proliferation of epidermal keratinocytes without any external antigenic factors.
authors.affiliation: Faculty of Medicine, Shiga University of Medical Science, Otsu, Japan. Electronic address: sugiurah@belle.shiga-med.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sugiura
authors.affiliation: Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Tazuke
authors.affiliation: R&D Department, Noevir, Higashiomi, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Bureau of International Medical Cooperation, National Center for Global Health and Medicinie, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kato
authors.affiliation: Diagnostic Pathology, Shiga University of Medical Science Hospital, Otsu, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Miyahira
authors.affiliation: R&D Department, Noevir, Higashiomi, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Faculty of Health and Human Life, Nagoya Bunri University, Inazawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Udagawa
authors.affiliation: Department of Dermatology, Yasu Hospital, Yasu, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Uehara
authors.affiliation: Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Japan; Sugiura Skin Clinic, Kusatsu, Japan. Electronic address: sugiura.clinic@iris.eonet.ne.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugiura
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000494:pharmacology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology; D004485:Eczema / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D050356:Lipid Metabolism; D026901:Membrane Transport Proteins; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D012463:Saliva / Q000201:enzymology; D013542:Sweat / Q000201:enzymology
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; C488892:PIP protein, human