Pancreas · 2025
Serum Exosomal miR-216a Contributes to Acute Pancreatitis-Associated Acute Lung Injury by Enhancing Endothelial Cell Vascular Permeability Through Downregulating LAMC1.
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Zhu Huiyun, Zhou Xianzhu, Sun Xingcheng, Fu Chunting, Li Ge, Dong Xiaoyang, Kong Xiangyu, Su Xiaoju, Du Yiqi
Аннотация
BACKGROUND: Acute pancreatitis (AP) is an internal medical emergency disease, with fatal complications including acute lung injury (ALI). Recent studies have highlighted the critical roles of exosomal microRNAs (miRNAs) in AP-ALI. In the present study, we aim to investigate the role of serum exosomal miR-216a in AP-ALI and its underlying mechanisms.
METHODS: The levels of miR-216a in patients and rat models with AP and AP-ALI were assessed through real-time quantitative PCR (qRT-PCR) analysis. Patient and rat blood exosomes were isolated and cocultured with HUVECs. The permeability of HUVECs was evaluated through transendothelial electrical resistance (TEER) assay. Bioinformatics predicting and luciferase reporter assays were used to identified potential targets of miR-216a. In addition, miR-216a mimic and LAMC1 overexpressed plasmid were constructed to identify the effects of miR-216a/LAMC1 axis on endothelial cell permeability in vitro. Anti-miR-216a and exosomes were used to identify the critical role of exosomal miR-216a in AP-ALI in vivo.
RESULTS: The findings indicated that there was a significant upregulation of miR-216a in AP-ALI patients and rat models. The occurrence of ALI during AP progression promoted the expression of serum exosomal miR-216a. Exosomal could promote HUVECs permeability by releasing miR-216a. For target studies, miR-216a was found to bind to LAMC1 to regulate its transcription level. MiR-216a-mediated downregulation of LAMC1 lead to increased permeability of HUVECs. Exosome-derived miR-216a has also been proved to promote lung damage in AP-ALI rats.
CONCLUSIONS: In summary, serum exosomal miR-216a can promote the onset and progression of AP-ALI by augmenting endothelial cell vascular permeability. This finding presents a theoretical basis for exploring new therapeutic approaches targeting AP-ALI.
METHODS: The levels of miR-216a in patients and rat models with AP and AP-ALI were assessed through real-time quantitative PCR (qRT-PCR) analysis. Patient and rat blood exosomes were isolated and cocultured with HUVECs. The permeability of HUVECs was evaluated through transendothelial electrical resistance (TEER) assay. Bioinformatics predicting and luciferase reporter assays were used to identified potential targets of miR-216a. In addition, miR-216a mimic and LAMC1 overexpressed plasmid were constructed to identify the effects of miR-216a/LAMC1 axis on endothelial cell permeability in vitro. Anti-miR-216a and exosomes were used to identify the critical role of exosomal miR-216a in AP-ALI in vivo.
RESULTS: The findings indicated that there was a significant upregulation of miR-216a in AP-ALI patients and rat models. The occurrence of ALI during AP progression promoted the expression of serum exosomal miR-216a. Exosomal could promote HUVECs permeability by releasing miR-216a. For target studies, miR-216a was found to bind to LAMC1 to regulate its transcription level. MiR-216a-mediated downregulation of LAMC1 lead to increased permeability of HUVECs. Exosome-derived miR-216a has also been proved to promote lung damage in AP-ALI rats.
CONCLUSIONS: In summary, serum exosomal miR-216a can promote the onset and progression of AP-ALI by augmenting endothelial cell vascular permeability. This finding presents a theoretical basis for exploring new therapeutic approaches targeting AP-ALI.