Zhou Yufeng’s team first revealed the function and regulatory mechanism of circular RNA in allergic dermatitis and psoriasis in the Journal of Allergy and Clinical Immunology

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 Atopic dermatitis (AD), also known as atopic dermatitis, is a chronic and recurrent skin inflammatory disease, with an incidence rate as high as 20-30% in children and 3-10% in adults
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The main clinical manifestations are impaired skin barrier function, itching and chronic skin inflammation

 Psoriasis, commonly known as psoriasis, is an autoimmune skin inflammatory disease with an incidence of 2-3%
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The clinical manifestations are mainly erythema and scaly

 Circular RNA (circRNA) is a research hotspot in the field of non-coding RNA in recent years, and it is also an emerging epigenetic regulation method, which has been reported to be involved in the occurrence and development of many diseases
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However, the role of circRNA in AD and psoriasis has not been reported yet

 The author first performed circRNA chip analysis on the peripheral blood mononuclear cells (PBMC) of AD patients, and screened the hsa_circ_0004287 molecules that were significantly up-regulated in AD patients.
Further studies found that hsa_circ_0004287 molecules were mainly derived from macrophages under inflammatory conditions, and hsa_circ_0004287 expressed The level is significantly negatively correlated with the expression level of IL-6, TNF-α and other inflammatory mediators in AD patients and the SCORAD score, suggesting that hsa_circ_0004287 may play an anti-inflammatory effect in AD (Figure 1)
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Figure 1.
The expression of hsa_circ_0004287 in PBMC of AD patients is up-regulated and negatively correlated with IL-6 and SCORAD

 Next, the authors constructed models of acute and chronic dermatitis in mice induced by calcipotriol (MC903) and 2,4-dinitrochlorobenzene (DNCB), and then applied the hsa_circ_0004287 overexpression plasmid locally with the help of in vivo transfection reagents To the skin of mice, the results showed that topical application of hsa_circ_0004287 plasmid significantly improved the skin inflammation in mice
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In order to further clarify that the therapeutic effect of hsa_circ_0004287 is exerted by macrophages, the author constructed the hsa_circ_0004287 plasmid specifically overexpressed by macrophages, and found that the local smearing of the hsa_circ_0004287 plasmid specifically overexpressed by macrophages also has the effect of alleviating inflammation ( Figure 2)

Figure 2.
Topical application of hsa_circ_0004287 overexpression plasmid significantly improved DNCB-induced dermatitis in mice

 Furthermore, the authors knocked down and overexpressed hsa_circ_0004287 in THP1-derived macrophages, Raw264.
7, and mouse bone marrow-derived macrophages (BMDM) to prove that hsa_circ_0004287 can inhibit LPS-induced M1 activation of macrophages
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Mechanism studies indicate that hsa_circ_0004287, which is located in the nucleus, promotes the degradation of MALAT1 by competing with its parent gene MALAT1 to bind to IGF2BP3 protein; and IGF2BP3, a classic m6A reader protein, can increase the stability of MALAT1 by recognizing the m6A site on MALAT1

 Finally, the authors found that the expression of hsa_circ_0004287 in the PBMC of patients with psoriasis was also up-regulated.

Figure 3.

 This study found for the first time the role of hsa_circ_0004287-IGF2BP3-MALAT1-S100A8/S100A9 axis in M1 macrophage activation and AD and psoriasis; for the first time, it revealed epigenetic factors in skin from two levels of circRNA and m6A modification.

 Doctoral student Yang Lan from the Institute of Biomedical Research of Fudan University, Attending Physician Fu Jinrong, Associate Researcher Han Xiao, and Assistant Researcher Zhang Caiyan from the Affiliated Pediatric Hospital are the co-first authors of this article; Researcher Zhou Yufeng and Professor Li Wei from the Department of Dermatology, Huashan Hospital are co-authors Corresponding author

Original link:

https://doi.