Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family

Abstract

In an effort to identify psoriasis-associated genes, we compared gene expression in normal and psoriatic skin, using differential display RT-PCR technique. Sequence analysis of a 650-bp cDNA fragment (clone 110) that was highly up-regulated in lesional skin revealed homology to a noncoding cDNA (NICE-2). By subsequent cDNA cloning, using RNA from psoriatic skin, we have identified two alternatively spliced mRNA-isoforms (0.5 and 4.4 kb), which differ in composition of their untranslated regions. By sequence comparison, we have mapped the novel gene, named S100A15, to the S100 gene cluster within the epidermal differentiation complex (chromosome 1q21). Analysis of the deduced amino acid sequence revealed a protein of 101 amino acids containing two potential EF-hand motifs with high homology to the S100A7. Northern blot hybridization and semiquantitative RT-PCR analysis confirmed the S100A15 overexpression in psoriasis, showing different levels of expression of the S100A15 mRNA isoforms. In situ hybridization of the S100A15 revealed a markedly increased staining of basal and suprabasal epidermal layers of psoriatic skin compared with healthy tissue. Our data suggest an involvement of the novel S100A15 in epidermal differentiation and inflammation and might therefore be important for the pathogenesis of psoriasis and other diseases.

The Antimicrobial Peptides Psoriasin (S100A7) and Koebnerisin (S100A15) Suppress Extracellular Matrix Production and Proliferation of Human Fibroblasts

“…Psoriasin and koebnerisin form a unique subgroup of the S100 protein family and were discovered to be up-regulated in psoriatic skin [17,29]. Although being highly homologous peptides, psoriasin and koebnerisin have distinct functions as epidermal antimicrobial peptides, leucocyte attractants and pro-inflammatory ‘alarmins' [18].…”

“…Koebnerisin (S100A15) protein shares 93% overall identity with psoriasin, with differences mainly concerning the deduced N-terminal Ca 2+ -binding site [17]. Koebnerisin expression is induced in cultured human keratinocytes upon treatment with tumour necrosis factor-α and interferon (IFN)-γ, and interleukin-1β, suggesting that the pro-inflammatory environment in diseased skin contributes to koebnerisin expression in the epidermis.…”

Antimicrobial skin peptides and proteins

“…Recently, in an effort to identify psoriasis-associated genes, a novel gene, named S100A15, with high homology to the S100A7 was discovered, which is also overexpressed in psoriasis [33]. Like psoriasin, S100A15 in situ hybridisation experiments revealed staining of epidermal layers of psoriatic skin, suggesting a similar function as psoriasin.…”

Differential gene expression of S100 protein family in leukocytes from patients with Kawasaki disease

“…S100 proteins are characterised by two distinct EFhand motifs displaying different affinities for calcium. An EF hand comprises a Ca 2+ binding loop which connects two helices, helices E and F. Of the S100 family of proteins, 23 members have been described [2,3,15,16,26]. S100 proteins are mainly localised in the cytosol, some of which have been shown to translocate from the cytosol to the membrane and cytoskeletal structures with elevations of intracellular calcium concentration [2,3].…”