Pathogenesis And Mechanism Underlying Treatment Of Psoriasis With Skin-derived Mesenchymal Stem Cells

NF-?B is constitutively activated in psoriatic epidermis.However,how activated NF-?B promotes keratinocyte hyperproliferation in psoriasis is largely unknown.Here we report that the NF-?B activation triggered by inflammatory cytokines induces the transcription of microRNA miR-31,one of the most dynamic microRNAs identified in the skin of psoriatic patients and mouse models.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 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,activated NF-?B inhibits ppp6c expression directly through the induction of miR-31,and enhances keratinocyte proliferation.Thus,our data identify NF-?B-induced miR-31 and its target,ppp6c,as critical factors for the hyperproliferation of epidermis in psoriasis.The study aims to explore the mechanisms of mesenchymal stem cells(MSCs)derived from skin of normal and inflammatory condition for their theaputic abilities.We investigated the changes of functions and therapeutic effects on psoriasis between MSCs derived from skin of normal and inflammatory conditions,the latter was established with imiquimod.The results revealed that MSCs from skin inflammatory microenvironment had enhanced proliferative and migratory capacities.Futhermore,the therapeutic effects of MSCs derived from IMQ-treated skin were more potent for the treatment of psoriasiform mouse models.While the anti-apoptosis capacity of SMSCs after IMQ treatment was decreased.In summary,we provide experimental basis and ideas for the establishment of a new strategy for the treatment of psoriasis.