Serum Exosomal miR-216a Contributes to Acute Pancreatitis-Associated Acute Lung Injury by Enhancing Endothelial cell Vascular Permeability via Downregulating LAMC1.

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 via real-time quantitative PCR (qRT-PCR) analysis. Patient and rat blood exosomes were isolated and co-cultured with HUVECs. The permeability of HUVECs was evaluated via trans-endothelial 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.
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