Highly complex peptide aggregates of the S100 fused-type protein hornerin are present in human skin.
Human hornerin (HRNR) is a 245 kDa S100 fused-type protein which contains 95% tandem quasi-repeating glycine- and serine-rich domains. Previously HRNR was not thought to be expressed in healthy skin; however, we purified an HRNR peptide fragment from stratum corneum. Moreover, we found that HRNR mRNA is expressed in skin biopsies from different sites as head, trunk, legs, hands, and feet. In cultured human epidermal keratinocytes, HRNR mRNA expression was transiently induced during Ca(2+)-dependent differentiation. Immunostaining using distinct antibodies generated against four putative HRNR domains revealed strong HRNR immunoreactivity in healthy epidermis as well as in the entire outer root sheath of normal human scalp hair follicles. In lesions from psoriasis and atopic dermatitis patients, HRNR immunoreactivity was reduced compared with uninvolved skin of these patients. Electrospray ionization mass spectrometry and Western blot analyses revealed that HRNR is a highly degradable protein that forms complex high molecular weight peptide aggregates. Our findings suggest that HRNR is expressed in healthy skin and give insight into the complex biology of this protein. HRNR and its degradation products might contribute to the barrier function of healthy human skin.
Wu
Zhihong
Z
Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
Meyer-Hoffert
Ulf
U
Reithmayer
Katrin
K
Paus
Ralf
R
Hansmann
Britta
B
He
Yinghong
Y
Bartels
Joachim
J
Gläser
Regine
R
Harder
Jürgen
J
Schröder
Jens-Michael
JM
D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D002135:Calcium-Binding Proteins; C503908:HRNR protein, human; D007381:Intermediate Filament Proteins; D009418:S100 Proteins