TY - JOUR
T1 - Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages
AU - Fang, Haizong
AU - You, Peidong
AU - Lin, Shengzhe
AU - Wu, Yuwei
AU - Lin, Jiajing
AU - Hou, Zelin
AU - Liang, Feihong
AU - Chen, Changgan
AU - Wang, Zhiyuan
AU - Chen, Linlin
AU - Zhang, Shihan
AU - Chen, Xiaolan
AU - Zhao, Kui
AU - Lu, Fengchun
AU - Pan, Minggui
AU - Zhou, Yundong
AU - Yin, Chengliang
AU - Conde, João
AU - Huang, Heguang
AU - Pan, Yu
N1 - Funding Information:
This study was supported by the Joint Funds for the innovation of Science and Technology, Fujian province (2024Y9277 to Y.P.), Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital (2022XH025 to Y.P.) and National Natural Science Foundation of China (no. 82103310 to Y.P.). J.C. acknowledges the Funda\u00E7\u00E3o Ci\u00EAncia e Tecnologia, IP national support, through UID/04923 - Comprehensive Health Research Centre.
Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2025.
PY - 2025/10
Y1 - 2025/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105012981032
U2 - 10.1038/s41565-025-01979-0
DO - 10.1038/s41565-025-01979-0
M3 - Article
AN - SCOPUS:105012981032
SN - 1748-3387
VL - 20
SP - 1514
EP - 1525
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 10
ER -