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Late cornified envelope ( LCE ) proteins: distinct expression patterns of LCE 2 and LCE 3 members suggest nonredundant roles in human epidermis and other epithelia
Author(s) -
Niehues H.,
VlijmenWillems I.M.J.J.,
Bergboer J.G.M.,
Kersten F.F.J.,
Narita M.,
Hendriks W.J.A.J.,
Bogaard E.H.,
Zeeuwen P.L.J.M.,
Schalkwijk J.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14284
Subject(s) - biology , stratum granulosum , epidermis (zoology) , stratum corneum , microbiology and biotechnology , colocalization , human skin , genetics , anatomy
Summary Background Deletion of the late cornified envelope ( LCE ) proteins LCE 3B and LCE 3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis‐specific proteins, rather than being a single‐nucleotide polymorphism of uncertain significance. The biology of the 18‐member LCE family of highly homologous proteins has remained largely unexplored so far. Objectives To analyse LCE 3 expression at the protein level in human epithelia, as a starting point for functional analyses of these proteins in health and disease. Methods We generated the first pan‐ LCE 3 monoclonal antibody and provide a detailed analysis of its specificity towards individual LCE members. LCE 2 and LCE 3 expression in human tissues and in reconstructed human skin models was studied using immunohistochemical analyses and quantitative polymerase chain reaction. Results Our study reveals that LCE 2 and LCE 3 proteins are differentially expressed in human epidermis, and colocalize only in the upper stratum granulosum layer. Using an in vitro reconstructed human skin model that mimics epidermal morphogenesis, we found that LCE 3 proteins are expressed at an early time point during epidermal differentiation in the suprabasal layers, while LCE 2 proteins are found only in the uppermost granular layer and stratum corneum. Conclusions Based on the localization of LCE 2 and LCE 3 in human epidermis we conclude that members of the LCE protein family are likely to have distinct functions in epidermal biology. This finding may contribute to understanding why LCE 3B/C deletion increases psoriasis risk.