| First Author | Yan S | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7652 | PubMed ID | 26138368 |
| Mgi Jnum | J:224375 | Mgi Id | MGI:5662142 |
| Doi | 10.1038/ncomms8652 | Citation | Yan S, et al. (2015) NF-kappaB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun 6:7652 |
| abstractText | NF-kappaB is constitutively activated in psoriatic epidermis. However, how activated NF-kappaB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-kappaB 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-kappaB activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-kappaB-induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis. |
