Genes Involved in Epithelial Differentiation and Development are Differentially Expressed in Oral and Genital Lichen Planus Epithelium Compared to Normal Epithelium

Abstract

Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

Genes involved in keratinization, keratinocyte and epithelium differentiation are aberrantly regulated in oral lichen planus

“…Small proline-rich protein 2B (SPRR2B) is a component of the cornified cell envelope of stratified squamous epithelia (Tarcsa et al 1998), which is also involved in epithelial differentiation (Zimmermann et al 2005). It should be noted that epithelium differentiation is closely associated with OLP, and keratinization is one of the classical features of OLP (Ismail et al 2007;Danielsson et al 2014). In this study, the expression of SPRR2B, CDSN, and LCEs was significantly up-regulated in OLP, coinciding with previous studies (Danielsson et al 2014).…”

“…It should be noted that epithelium differentiation is closely associated with OLP, and keratinization is one of the classical features of OLP (Ismail et al 2007;Danielsson et al 2014). In this study, the expression of SPRR2B, CDSN, and LCEs was significantly up-regulated in OLP, coinciding with previous studies (Danielsson et al 2014). Therefore, we suspected that CDSN, LCE3D, LCE3E, and SPRR2B might play a role in OLP through participating in keratinization, differentiation and development of keratinocyte and epithelium.…”

“…In addition, CDSN, LCE3D, LCE3E, SPRR2B were enriched in keratinization, differentiation and development of keratinocyte and epithelium. Reportedly, CDSN, LCEs, and SPRR2B are all part of the epidermal differentiation complex (EDC) (Gudjonsson et al 2009;Danielsson et al 2014). Corneodesmosin (CDSN) is a major component of corneodesmosomes, which localize to cornified human squamous epithelia and play an important role in maintaining epidermis integrity (Wada et al 2014).…”

“…Based on the gene expression data of epithelium from OLP patients and healthy controls (Gene Expression Omnibus (GEO) accession number: GSE52130), genes involved in epithelial development and differentiation are differentially expressed between OLP patients and normal controls, including LCE, CDSN, LOR, S100A7A, FLG, ASPRV1, RPTN, and KRT4 (Danielsson et al 2014). Furthermore, based on the gene expression data of primary oral mucosa tissues from OLP patients and healthy controls (GEO accession number: GSE38616), Gassling et al have identified 11 differentially expressed miRNA-mRNA pairs, of which miR-155-COL21A1, miR-let7i-MADCAM-1, and miR-132-RPS9 are mainly involved in premalignant and inflammatory progresses (Gassling et al 2013).…”

Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus

“…Previous investigations have shown that epithelial expression of keratins is altered in OLP compared with normal oral mucosa and this can therefore affect the functions mentioned above: keratin 1 (K1)/keratin 10 (K10) , K14 , keratin 6 (K6)/keratin 16 (K16), and K19 are reported to be upregulated in OLP, whereas keratin 4 (K4) , K4/keratin 13 (K13) , keratin 5 (K5)/keratin 15 (K15) , and K19 are reported to be downregulated. Data on K8 and K18 expression in oral keratinocytes of normal oral mucosa are inconsistent, varying from reports of absence to sporadic presence .…”