Highly Complex Peptide Aggregates of the S100 Fused-Type Protein Hornerin Are Present in Human Skin

Abstract

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.

Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases

“…SFTP genes consist of three exons, a tiny untranslated exon 1, a small exon 2 containing the translation start site and encoding a 46-residue S100 domain, and a large exon 3 encoding an EF-hand domain and internal tandem repeats, which are characteristic of cornified envelope precursor proteins. Recently a repeat domain of hornerin was identified in human stratum corneum (Wu et al 2009b), pointing to a proteolytic processing of this 245-kDa protein, which contains 95% tandem quasirepeating glycine-and serine-rich domains. It was reported that the proteolytic products of hornerin form high-molecular aggregates which might have special characteristics such as water-binding and elastic properties.…”

Kallikrein-related Peptidase 5 Functions in Proteolytic Processing of Profilaggrin in Cultured Human Keratinocytes

“…This sequence is specific for human pro-filaggrin and shows no homology to mouse or human hornerin (25,26) or filaggrin-2 (27). Antibodies were purified using antigen-coupled affinity chromatography.…”

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

“…The following antibodies were used: antibodies against filaggrin (1:6000; Biomedical Technologies Inc.); loricrin (1:500; BabCO); involucrin (1:50; Mon150; generated by our lab, van Duijnhoven [1992], University of Geneva, Switzerland); and hornerin (antibody was raised against full-length recombinant HRNR repeat domains, 1:200; ref. 59). For translocation of AHR and NRF2 (1:200, Santa Cruz), direct immunofluorescence labeling was performed using Alexa Fluor 488 conjugate in conjunction with fluorescence microscopy, and fluorescence intensity of nuclei and cytoplasm was measured by ImageJ software.…”