TLR4型
巨噬细胞极化
体内
化学
伤口愈合
细胞生物学
癌症研究
体外
巨噬细胞
磷酸化
药理学
医学
信号转导
生物化学
免疫学
生物
生物技术
作者
Yitong Liu,Gui‐Yang Xia,Yingyi Chen,Huan Xia,Junji Xu,Lijia Guo,Sheng Lin,Yi Liu
标识
DOI:10.1016/j.apsb.2023.05.032
摘要
Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.
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