Integrative analyses reveal biological pathways and key genes in psoriasis

Dou, Jinfa; Zhang, L.; Xie, Xuefeng; Ye, L.; Chun, Yang; Wen, Leilei; Shen, Changbing; Zhu, Caihong; Zhao, Suli; Zhu, Zhengwei; Liang, Bo; Wang, Z.; Li, H.; Fan, Xing; Liu, S.; Yin, Xianyong; Zheng, Xiaodong; Sun, Liang; Yang, Sen; Cui, Yiyao; Zhou, Fusheng; Zhang, X.

doi:10.1111/bjd.15682

Cited by 30 publications

(35 citation statements)

References 49 publications

(57 reference statements)

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“…Earlier studies have revealed five genes essential for psoriasis development: PPARD , GATA3 , TIMP3 , WNT5A and PTTG1 . In the present study, we also found an altered expression of PPARD , GATA3 and WNT5A .…”

Section: Discussionsupporting

confidence: 86%

“…Earlier studies have revealed five genes essential for psoriasis development: PPARD, GATA3, TIMP3, WNT5A and PTTG1. [34] In the present study, we also found an altered expression of PPARD, GATA3 and WNT5A. As a corollary, we note that a PPARβ/δ agonist has recently been shown to induce CERS3 and ELOVL4 in cultured keratinocytes.…”

Section: Effects On Other Genes Related To Keratinocyte Differentiasupporting

confidence: 85%

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Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Zhang

Ericsson

Weström

et al. 2018

Experimental Dermatology

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Autosomal recessive congenital ichthyosis (ARCI) is a group of monogenic skin disorders caused by mutations in any of at least 12 different genes, many of which are involved in the epidermal synthesis of ω‐O‐acylceramides (acylCer). AcylCer are essential precursors of the corneocyte lipid envelope crosslinked by transglutaminase‐1 (TGm‐1), or a yet unidentified enzyme, for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations will lead to a compensatory overexpression of the transcripts involved in skin barrier repair, including many other ARCI‐causing genes. Using microarray, we examined the global mRNA expression profile in skin biopsies from five ARCI patients with TGM1 mutations and four healthy controls. There were a total of 599 significantly differentially expressed genes (adjusted P < 0.05), out of which 272 showed more than 1.5 log2fold‐change (FC) up‐ or down‐regulation. Functional classification of the latter group of transcripts showed enrichment of mRNA encoding proteins mainly associated with biological pathways involved in keratinocyte differentiation and immune response. Moreover, the expression of seven out of twelve ARCI‐causing genes was significantly increased (FC = 0.98‐2.05). Also, many of the genes involved in keratinocyte differentiation (cornified envelope formation) and immune response (antimicrobial peptides and proinflammatory cytokines) were upregulated. The results from the microarray analysis were also verified for selected genes at the mRNA level by qPCR and at the protein level by semi‐quantitative immunofluorescence. The upregulation of these genes might reflect a compensatory induction of acylCer biosynthesis as a part of a global barrier repair response in the patient′s epidermis.

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Section: Discussionsupporting

confidence: 86%

Section: Effects On Other Genes Related To Keratinocyte Differentiasupporting

confidence: 85%

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Zhang

Ericsson

Weström

et al. 2018

Experimental Dermatology

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“…With growing sample sizes, the number of detected DEGs likewise increased. Ingenuity Pathway Analysis (IPA) or similar approaches revealed the frequent upregulation of "Cancer pathways", "Metabolic diseases", and "Cardiovascular diseases" reflecting the characteristics of psoriasis [19,20]. For example, the upregulation of "Cancer pathways" is an interesting finding as several phenotypic features like hyperproliferative keratinocytes with a low degree of differentiation argue in this direction.…”

Section: Emerging Technologiesmentioning

confidence: 99%

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

Schwingen

Kaplan

Kurschus

2020

IJMS

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During the last decades, high-throughput assessment of gene expression in patient tissues using microarray technology or RNA-Seq took center stage in clinical research. Insights into the diversity and frequency of transcripts in healthy and diseased conditions provide valuable information on the cellular status in the respective tissues. Growing with the technique, the bioinformatic analysis toolkit reveals biologically relevant pathways which assist in understanding basic pathophysiological mechanisms. Conventional classification systems of inflammatory skin diseases rely on descriptive assessments by pathologists. In contrast to this, molecular profiling may uncover previously unknown disease classifying features. Thereby, treatments and prognostics of patients may be improved. Furthermore, disease models in basic research in comparison to the human disease can be directly validated. The aim of this article is not only to provide the reader with information on the opportunities of these techniques, but to outline potential pitfalls and technical limitations as well. Major published findings are briefly discussed to provide a broad overview on the current findings in transcriptomics in inflammatory skin diseases.

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“…Since all PPARs are widely expressed in human skin and its appendages, there is increasing interest in their role in maintaining cutaneous homeostasis and in dermatological disorders . PPAR‐mediated signalling has attracted special interest in psoriasis, atopic dermatitis, acne, skin ageing, scleroderma, melasma, lipodystrophy and skin cancer . In the context of this Focus Theme Issue , this development encourages one to also take a closer look at why and how exactly PPARs are of special interest in a translational hair research context, with a strict focus on their best‐investigated isoform, PPAR‐γ.…”

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

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Integrative analyses reveal biological pathways and key genes in psoriasis

Abstract: Our analyses showed that genes contributed to the pathogenesis of psoriasis by activating risk pathways with components abnormality in expression. We identified five potentially pathogenic genes for psoriasis that may serve as important biomarkers for the diagnosis and treatment.

Cited by 30 publications

References 49 publications

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

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