Caiwei Zhuang, Qiulin Dong, Minjie Liu, Ying Tuo, Peishan Chen, Jiaying Li, Si Liu, Renchu Liu, Xuzhuo Cheng, Ruiyang Li, Sheng Wang, Shiyun Huang, Yufeng Liu, Rui Zhang, Andy Peng Xiang, Ge Shi, Mei Hua Jiang
Cutaneous nerve fibers play a significant regulatory role in psoriasis progression, with periostin (POSTN) acting as a key molecule in the neuro-immune-cutaneous axis. Using patient samples, neuronal cultures, and Postn -/- mice, we investigated the role of POSTN through molecular, histological, and transcriptomic analyses. Results demonstrated that POSTN is upregulated in psoriatic epidermis and dermis. Conversely, Postn -/- mice displayed alleviated psoriasis-like symptoms, decreased cutaneous nerve fiber density, and reduced nociceptive dorsal root ganglia (DRG) neurons with impaired neurite complexity. Mechanistically, POSTN promotes axonal growth by activating the PI3K/AKT/mTOR signaling pathway. Furthermore, applying cilengitide gel improved psoriatic skin lesions. Ultimately, this study identifies POSTN as a crucial regulator of cutaneous nerve fiber growth during psoriasis progression, highlighting its promise as a therapeutic target.