2. Academic Validation
  3. OASL activates MAPK to drive psoriatic pathogenesis: Astilbin targeting this axis improves metabolic-inflammation crosstalk

OASL activates MAPK to drive psoriatic pathogenesis: Astilbin targeting this axis improves metabolic-inflammation crosstalk

  • Life Sci. 2025 Aug 15:375:123698. doi: 10.1016/j.lfs.2025.123698.
Qingyue Xia 1,  Xiaoyi Huang 2,  Ang Li 3,  Zhou Zhuang 4,  Xinzhu Zhou 5,  Yue Yang 6,  Xianbo Zuo 7,  Yi Liu 8,  Yujun Sheng 9,  Jingkai Xu 10,  Yong Cui 11
Affiliations

Affiliations

  • 1 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China. Electronic address: b2023023014@pumc.edu.cn.
  • 2 Institute of Dermatology and Department of Dermatology of the First Affiliated Hospital, Anhui Medical University, Hefei 230031, China.
  • 3 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China.
  • 4 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; Peking University China-Japan Friendship School of Clinical Medicine Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.
  • 5 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; Peking University China-Japan Friendship School of Clinical Medicine Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: 2211210677@stu.pku.edu.cn.
  • 6 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; China-Japan Friendship Institute of Clinical Medical Sciences, Beijing 100029, China.
  • 7 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.
  • 8 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; Capital Medical University, Beijing 100069, China.
  • 9 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China; Institute of Dermatology and Department of Dermatology of the First Affiliated Hospital, Anhui Medical University, Hefei 230031, China. Electronic address: shengyujun@zryhyy.com.cn.
  • 10 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: xujingkai@zryhyy.com.cn.
  • 11 Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: cuiyong@zryhyy.com.cn.
PMID: 40360089 DOI: 10.1016/j.lfs.2025.123698
Abstract

Aims: This study aimed to elucidate the role of oligoadenylate synthase-like protein (OASL) as a pivotal regulator integrating keratinocyte hyperproliferation, inflammation, and lipid metabolic dysregulation in psoriasis pathogenesis.

Materials and methods: Clinical analyses compared epidermal OASL expression levels between psoriasis patients and healthy individuals. Functional studies in HaCaT cells employed OASL knockdown and overexpression to assess effects on proliferation, inflammatory responses, and lipid metabolism. The JAK1-STAT1-OASL regulatory axis was investigated using the JAK1 Inhibitor Upadacitinib. The natural flavonoid Astilbin was screened as an OASL inhibitor, and its therapeutic efficacy was evaluated in imiquimod-induced psoriatic mice.

Key findings: OASL was significantly upregulated in psoriatic epidermis. Knockdown of OASL suppressed keratinocyte proliferation and inflammation, while its overexpression promoted hyperproliferation, inflammation, and lipid metabolic dysregulation via p38 MAPK pathway activation. Mechanistically, Upadacitinib reduced OASL expression by inhibiting STAT1, confirming the JAK1-STAT1-OASL axis. Astilbin markedly alleviated imiquimod-induced psoriasiform dermatitis in mice.

Significance: This study reveals OASL's pivotal regulatory role in psoriasis and its associated pathways, providing novel therapeutic targets and a potential natural drug candidate. These findings establish a theoretical foundation for developing multi-targeted strategies against psoriasis.

Keywords

Cellular proliferation; JAK-STAT; Lipid metabolism; MAPK; OASL; Psoriasis.

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