Regulation of the development of psoriasis by ASK1, a stress-responsive MAP kinase

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09787
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokyo Medical University
• Principal Investigator: Okubo Yukari 東京医科大学, 医学部, 教授 (40233530)
• Co-Investigator(Kenkyū-buntansha): 善本 隆之 東京医科大学, 医学部, 教授 (80202406)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ASK1 / 乾癬 / イミキモド 角化細胞 / 分化

Outline of Final Research Achievements

Psoriasis is a helper T 17 cell-dependent chronic inflammatory skin disease characterized by thickening and redness of the skin with keratinocytes hyperproliferation, skin inflammation associated with inflammatory cell infiltration in the epidermis and dermis. Apoptosis signal-regulating kinase 1(ASK1) is a ubiquitously expressed serine/threonine mitogen-associated protein kinase kinase kinase (MAP3K) that activates p38 and JNK signaling pathways. In the present study, we investigated the role of ASK1 in the development of imiquimod-induced psoriasiform dermatitis by using ASK1 deficient mice. ASK1 deficient mice showed exacerbated psorisaiform dermatitis with increased expression of inflammatory cytokines such as TNF-α and IL-17 and proliferation of keratinocytes but decreased apoptosis of them. The present results suggest that ASK1 may play a role for supporting the normal differentiation of keratinocytes, which is presumed to be inhibitory against the development of psoriasis.

Free Research Field

皮膚科学