Li Mengyan, Li Die, Zhang Yu, Wang Juan, Wang Shenglan, Zhao Hao, Wang Hanying, Zeng Xiaofeng, Xu Dan, Lyu Lechun
Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming 650500, Yunnan, China.
Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
Int J Biol Macromol. 2025 Apr;304(Pt 2):140825. doi: 10.1016/j.ijbiomac.2025.140825. Epub 2025 Feb 9.
Psoriasis is a common chronic skin disease characterized by hyperproliferation of keratinized cells and infiltration of inflammatory cells that affects many patients worldwide. There is no cure for psoriasis, and its pathogenesis has not yet been fully elucidated. Alterations in some TRIM family proteins have been demonstrated to be involved in the exacerbation of psoriasis, however, the molecular mechanism of TRIM14 in psoriasis is unknown. Here, we show that TRIM14 is highly expressed in psoriasis patients and is closely associated with the progression of psoriasis. A possible mechanism is that TRIM14 binds to TRAF3 and mediates the autophagic degradation of TRAF3 through the selective autophagy receptor NDP52, activating the NF-κB pathway. In addition, cannabidiol (CBD) can effectively inhibit the proliferation of keratinocytes, possibly by inhibiting the expression of TRIM14 and attenuating the continuous activation of the NF-κB pathway in psoriasis. CBD-loaded hydrogel microneedle patches significantly improved the symptoms of keratoderma thickening, erythema and desquamation in psoriatic mice and reduced the levels of inflammatory factors in psoriatic skin tissue and blood, as well as the spleen index compared with Tacrolimus cream (positive control). In summary, TRIM14, which is highly expressed in psoriasis patients, may be a potential target and provide new ideas for the treatment of psoriasis. In addition, the CBD hydrogel microneedle patches developed for TRIM14 has obvious therapeutic effects and provides a new option for future drug therapy for psoriasis patients.
银屑病是一种常见的慢性皮肤病，其特征为角质形成细胞过度增殖和炎症细胞浸润，影响着全球众多患者。银屑病无法治愈，其发病机制尚未完全阐明。已证实一些TRIM家族蛋白的改变与银屑病的加重有关，然而，TRIM14在银屑病中的分子机制尚不清楚。在此，我们表明TRIM14在银屑病患者中高表达，且与银屑病的进展密切相关。一种可能的机制是，TRIM14与TRAF3结合，并通过选择性自噬受体NDP52介导TRAF3的自噬降解，从而激活NF-κB通路。此外，大麻二酚（CBD）可能通过抑制TRIM14的表达并减弱银屑病中NF-κB通路的持续激活，有效抑制角质形成细胞的增殖。与他克莫司乳膏（阳性对照）相比，负载CBD的水凝胶微针贴片显著改善了银屑病小鼠的角化过度增厚、红斑和脱屑症状，并降低了银屑病皮肤组织和血液中的炎症因子水平以及脾脏指数。总之，在银屑病患者中高表达的TRIM14可能是一个潜在靶点，并为银屑病的治疗提供新思路。此外，针对TRIM14开发的CBD水凝胶微针贴片具有明显的治疗效果，为未来银屑病患者的药物治疗提供了新选择。
