Plasma exosomal miR-25-3p alleviates acute pancreatitis-associated lung injury by inhibiting ferroptosis of type II alveolar epithelial cells via NOX4/NCOA4-mediated ferritinophagy
5 affiliations
- 1Department of Oncology Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
- 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
- 3Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
- 4Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
- 5Department of Gastrointestinal Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
Abstract
Background and objectives
Acute pancreatitis-associated lung injury (AP-LI) is a severe complication with limited therapeutic options. This study investigated the role of plasma exosomes in AP-LI and the underlying molecular mechanism.Methods
A murine AP-LI model and primary alveolar type II epithelial (AT2) cells were used. Small RNA sequencing, bioinformatic and enrichment analyses, functional assays, and in vivo and in vitro rescue experiments were performed to identify key exosomal miRNAs and define their downstream signaling pathways.Results
Plasma exosomes aggravated AP-LI. Small RNA sequencing revealed marked alterations in exosomal miRNA profiles, with miR-25-3p identified as a key candidate associated with oxidative stress and ferroptosis. NADPH oxidase 4 (NOX4) was predicted and validated as a direct target of miR-25-3p. miR-25-3p suppressed NOX4 expression and attenuated ferroptosis in AT2 cells. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy acted downstream of NOX4, promoted iron dysregulation, and reinforced ferroptotic injury. Rescue experiments confirmed the protective role of the miR-25-3p/NOX4/NCOA4 axis.Conclusions
Plasma exosomal miR-25-3p alleviates AP-LI by repressing NOX4 and limiting NCOA4-mediated ferritinophagy and ferroptosis, suggesting a potential therapeutic target for pulmonary complications of acute pancreatitis.
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BibTeX
@article{wang2026plasma,
title = {{Plasma exosomal miR-25-3p alleviates acute pancreatitis-associated lung injury by inhibiting ferroptosis of type II alveolar epithelial cells via NOX4/NCOA4-mediated ferritinophagy}},
author = {Zixin Wang and Zijian Huang and Jiafu Wang and Liang Zhang and Long Cheng and Meng He and Xuchen Hu and Junpeng Wu and Yusen Feng and Liang Ji and Yan Jin and Gang Wang},
journal = {Journal of translational internal medicine},
year = {2026},
month = oct,
doi = {10.1515/jtim-2026-0071},
url = {https://europepmc.org/article/PMC/PMC13726662},
note = {CC BY},
}
RIS
TY - JOUR
TI - Plasma exosomal miR-25-3p alleviates acute pancreatitis-associated lung injury by inhibiting ferroptosis of type II alveolar epithelial cells via NOX4/NCOA4-mediated ferritinophagy
AU - Zixin Wang
AU - Zijian Huang
AU - Jiafu Wang
AU - Liang Zhang
AU - Long Cheng
AU - Meng He
AU - Xuchen Hu
AU - Junpeng Wu
AU - Yusen Feng
AU - Liang Ji
AU - Yan Jin
AU - Gang Wang
PY - 2026
DA - 2026/10/23
JO - Journal of translational internal medicine
DO - 10.1515/jtim-2026-0071
UR - https://europepmc.org/article/PMC/PMC13726662
AB - Background and objectives Acute pancreatitis-associated lung injury (AP-LI) is a severe complication with limited therapeutic options. This study investigated the role of plasma exosomes in AP-LI and the underlying molecular mechanism.Methods A murine AP-LI model and primary alveolar type II epithelial (AT2) cells were used. Small RNA sequencing, bioinformatic and enrichment analyses, functional assays, and in vivo and in vitro rescue experiments were performed to identify key exosomal miRNAs and define their downstream signaling pathways.Results Plasma exosomes aggravated AP-LI. Small RNA sequencing revealed marked alterations in exosomal miRNA profiles, with miR-25-3p identified as a key candidate associated with oxidative stress and ferroptosis. NADPH oxidase 4 (NOX4) was predicted and validated as a direct target of miR-25-3p. miR-25-3p suppressed NOX4 expression and attenuated ferroptosis in AT2 cells. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy acted downstream of NOX4, promoted iron dysregulation, and reinforced ferroptotic injury. Rescue experiments confirmed the protective role of the miR-25-3p/NOX4/NCOA4 axis.Conclusions Plasma exosomal miR-25-3p alleviates AP-LI by repressing NOX4 and limiting NCOA4-mediated ferritinophagy and ferroptosis, suggesting a potential therapeutic target for pulmonary complications of acute pancreatitis.
SN - 2450-131X
SN - 2224-4018
ER -