2. Academic Validation
  3. Paeoniflorin-6'-O-benzene sulfonate inhibits keratinocyte proliferation by restoring GRK2-JAK1 colocalization in mouse model of psoriasis

Paeoniflorin-6'-O-benzene sulfonate inhibits keratinocyte proliferation by restoring GRK2-JAK1 colocalization in mouse model of psoriasis

  • Cell Signal. 2025 Mar 2:131:111706. doi: 10.1016/j.cellsig.2025.111706.
Tian Tian 1,  Mengzhu Wei 1,  Yanling Guan 1,  Lulu Rao 1,  Tingting Luo 1,  Chenchen Han 2,  Wei Wei 3,  Yang Ma 4
Affiliations

Affiliations

  • 1 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei 230032, China.
  • 2 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei 230032, China. Electronic address: chenchenhan@ahmu.edu.cn.
  • 3 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei 230032, China. Electronic address: wwei@ahmu.edu.cn.
  • 4 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei 230032, China. Electronic address: mayang_ahmu@126.com.
PMID: 40037425 DOI: 10.1016/j.cellsig.2025.111706
Abstract

Psoriasis is chronic inflammatory skin disease mediated by interactions between Th17 cells and keratinocytes that lead to excessive proliferation of keratinocytes, suggesting that anti-inflammatory and anti-proliferation molecules may be effective for the treatment. Paeoniflorin-6'-O-benesulfonic acid (CP-25), an esterified modifier of paeoniflorin, has exhibited potent anti-inflammatory and immunomodulatory properties in arthritis animal models and experimental Sjögren's syndrome. However, the involvement of CP-25 and its target G protein-coupled receptor kinase 2 (GRK2) in the development of psoriasis has not been explored. In this study, we found that GRK2 expression was abnormally elevated in the skin tissues of both psoriasis patients and imiquimod-induced psoriasis model mice. Furthermore, its inhibitor CP-25 reduced skin damage and systemic inflammation in model mice. Mechanically, CP-25 inhibited GRK2 translocation to the cytomembrane, thus decreasing colocalization of GRK2 and the βγ subunit of G protein (Gβγ), increasing colocalization of GRK2 with Janus kinase 1 (JAK1), and downregulating the JAK1-signal transduction and activator of transcription (STAT3) signaling pathway to reduce the hyperproliferation of keratinocytes, besides, CP-25-mediated inhibition of GRK2 translocation to the cytomembrane involved the GRK2 amino acid alanine 321 in keratinocytes. Our findings indicate that targeting GRK2 with CP-25 is a promising treatment for psoriasis.

Keywords

CP-25; GRK2; JAK1; Psoriasis.

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