2026-11-02 · 原文发表于 2026-09-19
靶向USP47可调节巨噬细胞极化，改善脓毒性腹膜炎和皮肤创面愈合
Lei H, Yang L, Xu H, Wang Y, Wu Y.. Targeting USP47 reprograms macrophage polarization to ameliorate septic peritonitis and promote cutaneous wound healing. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2026;75(1):220. doi:10.1007/s00011-026-02380-w. PMID:42762317.
查看原始文献（Europe PMC · 创面修复文献）↗研究问题
巨噬细胞的M1/M2极化失衡与脓毒症和创面愈合不良密切相关。去泛素化酶（DUBs）是潜在的药物靶点，但USP47在巨噬细胞可塑性中的作用尚不明确。
研究设计
主要发现
如何理解
局限与不确定性
一句话带走
抑制USP47可能通过调节巨噬细胞极化改善炎症性疾病，但其在人体中的疗效和安全性仍需进一步研究。该研究为开发靶向USP47的治疗策略提供了机制依据。
术语小注
- 巨噬细胞极化：
- 巨噬细胞根据功能状态分为M1（促炎）和M2（抗炎/修复）型，其平衡影响炎症和组织修复过程。
- 去泛素化酶：
- 一类可去除蛋白质上泛素标签的酶，影响蛋白质稳定性与功能，如USP47属于此类。
- YAP蛋白：
- 一种转录共激活因子，参与细胞增殖、凋亡和炎症反应，可被USP47调控稳定。
- NLRP3炎症小体：
- 一种多蛋白复合物，可激活炎症反应，与多种炎症性疾病相关。
- 泛素化：
- 一种蛋白质修饰过程，通过添加泛素分子调节蛋白质稳定性、定位和功能。
- 脓毒性腹膜炎：
- 由细菌感染引起的腹膜炎症，常导致全身炎症反应综合征和器官功能障碍。
展开原文摘要
Objective Dysregulation of M1/M2 macrophage polarization drives sepsis and impaired wound healing. Deubiquitinases (DUBs) are promisingdrug targets, but the role of ubiquitin-specific protease 47 (USP47) in macrophage plasticity remains unclear. This study investigated the regulatoryfunction of USP47 in macrophage polarization and its therapeutic potential for inflammatory disorders. Methods In vitro, human THP-1 and mouse bonemarrow-derived macrophages were polarized, with USP47 modulated via genetic manipulation or the inhibitor P22077. In vivo, LPS-induced septicperitonitis and cutaneous wound models were used to evaluate the effects of Usp47 deficiency or P22077 treatment. Mechanistically, protein interactionand ubiquitination assays were performed to verify the USP47-YAP axis and downstream signaling. Results USP47 was upregulated in M1 macrophagesand downregulated in M2 macrophages. USP47 inhibition skewed macrophages toward the M2 phenotype. In vivo , Usp47 knockout or P22077 treatmentimproved survival in septic mice, reduced systemic inflammation, and accelerated wound healing, accompanied by increased M2 infiltration at lesion sites.Mechanistically, USP47 directly deubiquitinated and stabilized YAP protein; stabilized YAP drove M1 polarization via two parallel axes: nucleartranslocation to promote pro-inflammatory cytokine transcription, and promotion of NLRP3 inflammasome stabilization. Conclusions USP47 is a critical regulator of macrophage polarization via the USP47-YAP-NLRP3 axis. Targeting USP47 exerts anti-inflammatory and pro-repair effects, representing a promising therapeutic strategy for sepsis and wound healing disorders.
本站中文摘要：这项前临床研究在巨噬细胞体外实验及动物脓毒性腹膜炎、皮肤创面模型中发现，抑制USP47促进M2型极化，Usp47缺失或P22077处理加快创面愈合，并伴随病灶处M2型巨噬细胞浸润增加。