TGF-β信号通路在银屑病中具有抗炎作用，但其活性在病变皮肤中是下调的。角蛋白17是在正常表皮不表达而在银屑病皮损中高表达的Ⅰ型角蛋白，被认为是银屑病相关角蛋白。银屑病病情的缓解往往伴随K17表达的下调，因此研究K17负向调控机制具有重要的临床意义。我们前期研究发现miR-486-3p在银屑病皮损中的表达显著低于正常对照，且具有负向调控K17的功能。进一步的生物信息学分析发现，miR-486-3p初始体存在TGF-β信号传导通路下游转录因子SMADs的潜在结合位点。本课题拟在此基础上，利用细胞和生物学技术结合体外实验和动物模型来验证：TGF-β/SMADs/miR-486-3p通路对K17转录后的互相调控机制。并阐明在银屑病中，TGF-β/SMADs信号通路活性下调，使miR-486-3p成熟体形成减少，从而导致K17的升高和病情恶化的病理机制，为银屑病个体化治疗和新药研发提供重要参考。

TGF-β signaling is downregulated and has been shown an anti-inflammatory role in Psoriasis. Kerain 17 (K17) is a type I keratin protein that has a high expression in Psoriasis lesions but not in normal epidermis. K17 has been considered as a "Psoriatic protein". Downregulation of K17 expression is usually correlated to the remission of Psoriasis, thus it is of great clinical significance to reveal the molecular mechanism(s) underlying the downregulation of K17. Our previous study has shown that a microRNA molecule, miR-486-3p, is downregulated significantly in Psoriatic lesions and can directly suppress K17 expression. Further bioinformatics study reveals a potential SMADs binding motif in miR-486-3p. Thus we hypothesize that TGF- β signaling activates SMADs, promotes the conversion of pri-miR-486-3p to pre-miR-486-3p, and suppresses the expression of K17. In Psoriasis, TGF-βsignaling is suppressed, causing decrease in phosphorylation level of SMADs and formation of mature miR-486-3p, and finally leading to increase in expression of K17. In this proposal, we will use a series of molecular biology, cell biology approaches and in vivo Psoriatic animal model to examine the TGF- β/SMADs/miR-486-3p/K17 signaling and its role in the suppression of the expression of K17 ,attenuate the progression of Psoriasis and provide a new effective strategy for Psoriasis therapy.