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The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

ABSTRACT: Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients' quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients' measurable severity of illness, as well as the impact the skin condition has on patients' quality of life, as assessed by standardized questionnaires. The clinical scales used nowadays for measuring the severity of psoriasis are characterized by low reproducibility and high variability between examiners. Hence, there is a real need to identify objectively measurable biomarkers to standardize the assessment of the severity of psoriasis. We aim to review the pathophysiological mechanisms involved in psoriasis, focusing on the most critical advances in psoriasis biomarker discovery, pointing out those biomarkers which have also been studied in other stress-related conditions, thus emphasizing the relationship between psoriasis and stress.

SUBMITTER: Tampa M

PROVIDER: S-EPMC5829341 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

Tampa Mircea M Sarbu Maria-Isabela MI Mitran Madalina-Irina MI Mitran Cristina-Iulia CI Matei Clara C Georgescu Simona-Roxana SR

Disease markers 20180128

Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients' quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients' measurable severity of illness, as well as the impact the skin condition has on p ...[more]

PMID: 29619128

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Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.

Dataset Information

The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

Publications

The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

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