Fang Haizong, You Peidong, Lin Shengzhe, Wu Yuwei, Lin Jiajing, Hou Zelin, Liang Feihong, Chen Changgan, Wang Zhiyuan, Chen Linlin, Zhang Shihan, Chen Xiaolan, Zhao Kui, Lu Fengchun, Pan Minggui, Zhou Yundong, Yin Chengliang, Conde João, Huang Heguang, Pan Yu
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
Department of Pathology, Second Hospital of Shandong University, Jinan, People's Republic of China.
Nat Nanotechnol. 2025 Aug 11. doi: 10.1038/s41565-025-01979-0.
Acute pancreatitis (AP) is associated with high mortality rates and is characterized by increased cell death of acinar cells, with the premature release and activation of digestive enzymes. In its acute phase, AP is accompanied by increased efferocytosis, to clear phagocytic apoptotic cells; annexin A1 (Anxa1) is key to efferocytosis, but its role in AP is still unknown. Here we show that Anxa1 deficiency abrogates the efferocytosis of pancreatic macrophages, resulting in the accumulation of apoptotic acinar cells and necrosis. Moreover, we showed that nano-liposomes loaded with Anxa1 mRNA alleviate AP pathology by suppressing the cGAMP-cGAS-STING pathway and restoring efferocytosis in macrophages. Our results reveal the crucial function of Anxa1 in the efferocytosis of macrophages during AP and illustrate a novel nanotechnology treatment approach for AP that may be of potential therapeutic value in humans.
急性胰腺炎（AP）与高死亡率相关，其特征是腺泡细胞的细胞死亡增加，同时消化酶过早释放和激活。在急性期，AP伴有吞噬作用增强，以清除吞噬性凋亡细胞；膜联蛋白A1（Anxa1）是吞噬作用的关键，但它在AP中的作用仍不清楚。在这里，我们表明Anxa1缺乏会消除胰腺巨噬细胞的吞噬作用，导致凋亡腺泡细胞的积累和坏死。此外，我们还表明，装载Anxa1 mRNA的纳米脂质体通过抑制cGAMP-cGAS-STING途径并恢复巨噬细胞的吞噬作用来减轻AP病理。我们的结果揭示了Anxa1在AP期间巨噬细胞吞噬作用中的关键功能，并阐明了一种新型的AP纳米技术治疗方法，该方法可能对人类具有潜在的治疗价值。
