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Mesenchymal stem cells in psoriatic lesions affect the skin microenvironment through circular RNA
Author(s) -
Liu Ruifeng,
Chang Wenjuan,
Li Juan,
Cheng Yueai,
Dang Erle,
Yang Xiaohong,
Wang Qiang,
Wang Gang,
Li Xinhua,
Zhang Kaiming
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13890
Subject(s) - rna , psoriasis , gene knockdown , circular rna , messenger rna , pathogenesis , mesenchymal stem cell , cancer research , non coding rna , microbiology and biotechnology , rna binding protein , biology , gene , immunology , genetics
Abstract Psoriasis is an autoimmune skin disease. Our previous studies revealed abnormal immune regulation of skin mesenchymal stem cells (S‐ MSC s) in psoriatic lesions. Circular RNA (circ RNA ) molecules were recently discovered as a new class of non‐coding regulatory RNA s. Their role in the pathogenesis of psoriasis has not yet been studied. To explore potential circ RNA ‐mediated mechanisms of S‐ MSC s in the pathogenesis of psoriasis, we sequenced mRNA s and circ RNA s of MSC s from normal skin and psoriatic lesions, followed by functional prediction and interaction analyses. In total, 129 circ RNA s were differentially expressed, including 123 up‐regulated and 6 down‐regulated circ RNA s, in MSC s from psoriatic lesions. Pathway analysis showed that the genes significantly down‐regulated in psoriatic as compared to normal S‐ MSC s were mainly involved in JAK ‐ STAT signalling. According to a circ RNA ‐mi RNA ‐ mRNA interaction network, the expression of circ RNA s associated with these mRNA s was also down‐regulated in MSC s of psoriatic skin lesions. Knockdown of the circ RNA gene chr2:206992521|206994966 reduced the capacity of S‐ MSC s to inhibit T‐cell proliferation upon co‐culture in normal as well as lesion‐derived S‐ MSC s. Secreted‐cytokine profiles ( IL ‐6, IL ‐11 and hepatocyte growth factor) were also similar in normal and lesion‐derived S‐ MSC s after circ RNA knockdown. Thus, the circ RNA chr2:206992521|206994966 in S‐ MSC s from psoriatic lesions affects the activity of T lymphocytes in local lesions by influencing their cytokine secretion. Taken together, our findings indicate that circ RNA mediates the role of S‐ MSC s in the pathogenesis of psoriasis.