Suppression of TP Rat Pancreatic Acinar Cell Apoptosis by hucMSC‐Ex Carrying hsa‐miR‐21‐5p via PTEN/PI3K Regulation

<b>Objective:</b> The traumatic pancreatitis (TP) has an alarmingly high mortality rate. Our previous research has demonstrated that human umbilical cord mesenchymal stem cells-derived exosomes (hucMSC-Exs) could treat TP by inhibiting acinar cell apoptosis. Accordingly, the objective of this study is to unravel the intricate mechanism behind the repair of pancreatic injury in TP rats. <b>Methods:</b> A gene interaction network of miRNA was constructed based on the Gene Expression Omnibus (GEO) database (GSE 159814). Our investigation was divided into two groups, and appropriate controls were implemented for each group. The expression levels of inflammatory factors in each group were detected, along with the pathological damage of pancreatic tissue, the percentage of apoptotic cells, and key mRNA and protein expression levels. <b>Results:</b> The miRNA-mRNA gene interaction network suggests that hsa-miR-21-5p/phosphatase and tensin homolog (PTEN) are positioned at the core of this interaction network. Enzyme-linked immunosorbent assay (ELISA) and histological examination (HE) results suggest that pancreatic damage increased in the miR-21 inhibitor and EXW groups, whereas it decreased in the miR-21 activator and EXC groups compared to the EX group. PCR, western blot (WB), and TdT-mediated dUTP Nick-End Labeling (TUNEL) results indicate that hucMSC-Ex carrying hsa-miR-21-5p suppresses excessive activation of PTEN by phosphoinositide 3-kinase (PI3K), exerting therapeutic effects. <b>Conclusion:</b> This study has discovered that hucMSC-Ex effectively inhibits the translation of PTEN via the transported hsa-miR-21-5p, consequently affecting the PI3K/serine-threonine kinase (AKT) signaling pathway. This results in reduced inflammation and inhibition of acinar cell apoptosis by regulating pancreatic enzyme leakage, thereby providing a therapeutic effect on TP.