Details

Autor(en) / Beteiligte

• Yu, Zengyang
• Yu, Qian
• Xu, Hui
• Dai, Xing
• Yu, Yingyuan
• Cui, Lian
• Chen, Youdong
• Gu, Jun
• Zhang, Xilin
• Guo, Chunyuan
• Shi, Yuling

Titel

IL-17A promotes Psoriasis-associated Keratinocyte Proliferation via ACT1-depedent Activation of YAP-AREG Axis

Ist Teil von

• Journal of investigative dermatology, 2022-03

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Psoriasis is a recurrent inflammatory skin disorder characterized by epidermal hyperplasia which is primarily driven by interleukin (IL)-17A. The Hippo-YAP signaling pathway plays a vital role in cell survival and tissue growth, and its target gene, AREG, has been reported to promote the development of psoriasis. However, whether IL-17A promotes keratinocyte proliferation via regulating Hippo-YAP signaling has not been explored. Here, we show that the YAP-AREG pathway is activated in human psoriatic skin and is suppressed by IL-17A antagonist secukinumab and that IMQ and IL-17A administration activates the YAP-AREG axis in mice epidermis. In vitro studies using HaCaT and NHEK cells suggest that IL-17A enhances AREG expression and keratinocyte proliferation by activating Hippo-YAP signaling. Mechanistically, IL-17A stimulates the recruitment of MST1 to ACT1 in keratinocytes, which leads to reduced MST1-LATS1 interaction and YAP dephosphorylation. Together, our findings reveal a previously unknown mechanism in which IL-17A promotes keratinocyte proliferation in psoriasis, namely through activating YAP-AREG signaling.