Systematic screening and identification of novel psoriasis‑specific genes from the transcriptome of psoriasis‑like keratinocytes

Abstract

Psoriasis is a chronic inflammatory skin disease. Keratinocytes (KCs), as skin-specific cells, serve an important role in the immunopathogenesis of psoriasis. In the present study, transcriptome data derived from psoriasis-like KCs were used together with the reported transcriptome data from the skin/epidermis of patient with psoriasis, excluding known psoriasis-associated genes that have been well described in the previous studies according to GeneCards database, to screen for novel psoriasis-associated genes. According to the human expressed sequence tag of UniGene dataset, six genes that are located near psoriasis-associated loci were highly expressed in skin. Among these six genes, four genes (epiregulin, NIPA like domain containing 4, serpin family B member 7 and WAP four-disulfide core domain 12) were highly expressed in normal mouse epidermis (mainly KCs) and mouse psoriatic epidermis cells, but not in psoriatic dermis cells, which further emphasized the specificity of these genes. Furthermore, in systemic inflammatory response syndrome (SIRS), SERPINB7 showed no difference in expression in immune-activated tissues from SIRS and control mice. It was also found that the mRNA expression levels of SERPINB in lesional skin of patients with psoriasis were significantly higher than in non-lesional psoriatic skin from the same patients. SERPINB7 may be a valuable candidate for further studies. In the present study, a method for identifying novel key pathogenic skin-specific molecules is presented, which may be used for investigating and treating psoriasis.

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

“…In this sense, the genes from the transcriptomic profile of cultured cytokine-stimulated keratinocytes overlapping with that of the lesional psoriasis skin only represented up to 5.0% of the psoriatic altered transcriptome [ 68 ]. Wang et al observed similar results regarding the proportion of deregulated genes overlapping between cultured cytokine-stimulated keratinocytes and lesional psoriatic skin while using HaCat keratinocytes, and thus showed once again the limitation of using monolayer systems to obtain a gene alteration profile that mimics the pathology in the most representative manner [ 118 ]. The lack of pathological keratinocytes in studies using these monolayer psoriatic-like models represents a major disadvantage for further transcriptomic studies.…”

Orchestrated Cytokines Mediated by Biologics in Psoriasis and Its Mechanisms of Action

“…The discovery of an effective novel biologic gives new insights into how beneficial it is to target important immune components, such as cytokines, in alleviating psoriasis exasperation. Hence, it can support other advanced methods, such as the quantification of numerous cytokines receptors using both mRNA and cDNA microarrays [ 43 , 44 ]. Thus, it is crucial to inhibit cytokine signaling if that is the attempted exit strategy for psoriasis.…”

“…TNF-α is a proinflammatory cytokine secreted by DCs, T cells, macrophages and non-immune cells, such as fibroblasts; therefore, its selection in the revolution of inhibitor drugs is promising [ 44 ]. TNF-α acts as the main mediator during the initiation phase of classical psoriasis and can sustain the disease over the long term [ 45 , 46 , 47 ].…”

Generalized pustular psoriasis (von Zumbusch)

“…Many genomic scanning studies replicated in different populations have demonstrated genetic polymorphisms associated with plaque psoriasis. 13 There are more than 50 chromosomal regions or loci of susceptibility to psoriasis, demonstrating the multigene and epigenetic interaction characteristic of the disease. 14 The genes whose polymorphisms confer susceptibility to plaque psoriasis are related to antigen presentation (ERAP1 and MHC), interferon signaling pathway (IL-28RA and IFIH1), NFkB pathway (ZNF313, REL, TNIP1, TNFAIP3, NFkB1A), 15 of IL-17 (TRAF3IP2), of IL-23 (TYK2, IL-23R, IL-23A, IL-12B) and to the epidermal barrier (LCE3D).…”