Abstract
To better understand the pathomechanism of psoriasis, a comparative proteomic analysis was performed with non-lesional and lesional skin from psoriasis patients and skin from healthy individuals. Strikingly, 79.9% of the proteins that were differentially expressed in lesional and healthy skin exhibited expression levels in non-lesional skin that were within twofold of the levels observed in healthy and lesional skin, suggesting that non-lesional skin represents an intermediate stage. Proteins outside this trend were categorized into three groups: I. proteins in non-lesional skin exhibiting expression similar to lesional skin, which might be predisposing factors (i.e., CSE1L, GART, MYO18A and UGDH); II. proteins that were differentially expressed in non-lesional and lesional skin but not in healthy and lesional skin, which might be non-lesional characteristic alteration (i.e., CHCHD6, CHMP5, FLOT2, ITGA7, LEMD2, NOP56, PLVAP and RRAS); and III. proteins with contrasting differential expression in non-lesional and lesional skin compared to healthy skin, which might contribute to maintaining the non-lesional state (i.e., ITGA7, ITGA8, PLVAP, PSAPL1, SMARCA5 and XP32). Finally, proteins differentially expressed in lesions may indicate increased sensitivity to stimuli, peripheral nervous system alterations, furthermore MYBBP1A and PRKDC were identified as potential regulators of key pathomechanisms, including stress and immune response, proliferation and differentiation.
Highlights
Our skin connects, and at the same time separates internal the external environment
Elevated expression of the anti-inflammatory regulator caspase recruitment domain family member 18 (CARD18) in non-lesional skin compared to healthy skin was found to aid the inhibition of inflammatory events[15]
The schematic overview of the applied proteomic strategy is summarized in Fig. 1, and basic demographic and clinical characteristics of psoriatic patients and healthy donors are listed in Table 1. (Criteria for inclusion of patients in the study and skin sample collection are described at Supplementary Material: Materials and Methods section)
Summary
At the same time separates internal the external environment. It is constantly subjected to many different stimuli that requires proper response, through which the skin can influences the function of other organs, like the brain and the endocrine system in a mutual way[1,2]. Elevated expression of the anti-inflammatory regulator caspase recruitment domain family member 18 (CARD18) in non-lesional skin compared to healthy skin was found to aid the inhibition of inflammatory events[15]. These mechanisms, among many others, highlight the relevance of comparing non-lesional skin to healthy skin. One of the most effective ways to study different diseases with such a high complexity and to elucidate related mechanisms is to perform a comparative proteomic analysis of protein extracts derived from affected tissues. A complex comparison was performed, where in addition to non-lesional and lesional skin, samples from healthy skin were included, in a label-free, semi-quantitative proteomic analysis
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