2. Academic Validation
  3. Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages

Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages

  • Nat Nanotechnol. 2025 Aug 11. doi: 10.1038/s41565-025-01979-0.
Haizong Fang # 1,  Peidong You # 1 2,  Shengzhe Lin # 3 4,  Yuwei Wu # 1 5,  Jiajing Lin # 1,  Zelin Hou # 1,  Feihong Liang 1 4,  Changgan Chen 1,  Zhiyuan Wang 1,  Linlin Chen 6,  Shihan Zhang 6,  Xiaolan Chen 7,  Kui Zhao 8,  Fengchun Lu 1,  Minggui Pan 9,  Yundong Zhou 10,  Chengliang Yin 11,  João Conde 12,  Heguang Huang 13,  Yu Pan 14 15
Affiliations

Affiliations

  • 1 Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
  • 2 Department of Pathology, Second Hospital of Shandong University, Jinan, People's Republic of China.
  • 3 Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
  • 4 Fujian Medical University Cancer Center, Fuzhou, People's Republic of China.
  • 5 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
  • 6 Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
  • 7 The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
  • 8 School of Nursing, Yunnan University of Chinese Medicine, Kunming, People's Republic of China.
  • 9 Stanford University School of Medicine, Palo Alto, CA, USA.
  • 10 The Second Department of Oncology, Huizhou First Hospital, Huizhou, People's Republic of China.
  • 11 Faculty of Medicine, Macau University of Science and Technology, Macau, People's Republic of China. chengliangyin@163.com.
  • 12 Comprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ciências Médicas, NMS
  • 13 joao.conde@nms.unl.pt.
  • 14 Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China. heguanghuang22@163.com.
  • 15 Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China. yupan199002@163.com.
  • 16 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China. yupan199002@163.com.
  • # Contributed equally.
PMID: 40789923 DOI: 10.1038/s41565-025-01979-0
Abstract

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.

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