期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8652
关键词
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资金
- 973 program
- National Natural Science Foundation of China [2012CB917100, 2014CB541905, 31330026, 81202304, 91029730]
- Leading Academic Discipline Project of the Shanghai Municipal Education Commission [J50208, J50207]
NF-kappa B is constitutively activated in psoriatic epidermis. However, how activated NF-kB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-kB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF-kappa B activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-kappa B-induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis.
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