Lin Zhengyi, Zhao Haiyi, Lin Haojie, Song Lanni, Tian Xuechen, Choo Siew Woh
College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, 325060, Zhejiang Province, China.
Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, 07083, NJ, USA.
Immunol Res. 2025 Jul 24;73(1):110. doi: 10.1007/s12026-025-09663-0.
Chronic inflammation underlies many diseases, posing challenges in therapeutic management due to the limitations and side effects of current treatments and necessitating novel therapeutic solutions. Here, we introduce PS77, a novel α-helical peptide derived from Squama Manitis, a Traditional Chinese Medicine, and unveil its remarkable anti-inflammatory properties, potentially revolutionizing biomaterials design for targeted anti-inflammatory therapies. An in vitro TNF-α-induced inflammatory model in human keratinocytes (HaCaT cells) was used to demonstrate PS77's significant impact. We demonstrated that PS77 significantly reduced IL-8 and MMP-3 expression, indicating potent anti-inflammatory activity without cytotoxicity to normal cells. Transcriptomic analysis further elucidated PS77's mechanism of action, revealing significant modulation of 265 genes (137 upregulated and 128 downregulated), with a particular focus on the downregulation of genes within the BMP and TGF-β signaling pathways-key players in inflammation. Moreover, PS77 regulated several inflammation-associated genes, including CHRNA7, CXCR5, RXRG, KRT76, IL12RB2, and COLEC11, underscoring its comprehensive anti-inflammatory effects. This study not only highlights PS77's therapeutic potential as a biomaterial for treating inflammatory diseases but also paves the way for further research into its mechanisms and applications in biomedicine. By leveraging the novel biomaterial properties of PS77, this research may contribute to the development of targeted and efficient anti-inflammatory therapies, marking a significant advance in the field of biomaterials and offering a promising avenue for inflammation management.
慢性炎症是许多疾病的基础，由于当前治疗方法的局限性和副作用，在治疗管理方面带来了挑战，因此需要新的治疗方案。在此，我们介绍了PS77，一种源自中药穿山甲的新型α-螺旋肽，并揭示了其显著的抗炎特性，这可能会彻底改变用于靶向抗炎治疗的生物材料设计。利用人角质形成细胞（HaCaT细胞）中的体外TNF-α诱导炎症模型来证明PS77的显著影响。我们证明PS77显著降低了IL-8和MMP-3的表达，表明其具有强大的抗炎活性且对正常细胞无细胞毒性。转录组分析进一步阐明了PS77的作用机制，揭示了265个基因的显著调节（137个上调和128个下调），特别关注BMP和TGF-β信号通路中基因的下调，这些通路是炎症中的关键参与者。此外，PS77调节了多个与炎症相关的基因，包括CHRNA7、CXCR5、RXRG、KRT76、IL12RB2和COLEC11，强调了其全面的抗炎作用。这项研究不仅突出了PS作为治疗炎症性疾病的生物材料的治疗潜力，也为进一步研究其在生物医学中的机制和应用铺平了道路。通过利用PS77的新型生物材料特性，这项研究可能有助于开发靶向且高效的抗炎治疗方法，标志着生物材料领域的重大进展，并为炎症管理提供了一条有前景的途径。
