Zhirong Zhao, Kexin Jiang, Mu Yuan, Lichen Zhou, Zhen Tan, Hongyin Liang, Ruiwu Dai
General Surgery Center, General Hospital of Western Theater Command, Chengdu, Sichuan Province, China.
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
Stem Cells Int. 2025 Mar 17;2025:8883585. doi: 10.1155/sci/8883585. eCollection 2025.
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. 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. 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. 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.
创伤性胰腺炎（TP）的死亡率高得惊人。我们之前的研究表明，人脐带间充质干细胞来源的外泌体（hucMSC-Exs）可通过抑制腺泡细胞凋亡来治疗TP。因此，本研究的目的是揭示TP大鼠胰腺损伤修复背后的复杂机制。基于基因表达综合数据库（GEO）（GSE 159814）构建了miRNA基因相互作用网络。我们的研究分为两组，每组都设置了适当的对照。检测了每组炎症因子的表达水平、胰腺组织的病理损伤、凋亡细胞百分比以及关键mRNA和蛋白质的表达水平。miRNA-mRNA基因相互作用网络表明，hsa-miR-21-5p/磷酸酶和张力蛋白同源物（PTEN）位于该相互作用网络的核心。酶联免疫吸附测定（ELISA）和组织学检查（HE）结果表明，与EX组相比，miR-21抑制剂组和EXW组的胰腺损伤增加，而miR-21激活剂组和EXC组的胰腺损伤减少。聚合酶链反应（PCR）、蛋白质免疫印迹（WB）和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）结果表明，携带hsa-miR-21-5p的hucMSC-Ex通过磷酸肌醇3激酶（PI3K）抑制PTEN的过度激活，发挥治疗作用。本研究发现，hucMSC-Ex通过转运的hsa-miR-21-5p有效抑制PTEN的翻译，从而影响PI3K/丝氨酸-苏氨酸激酶（AKT）信号通路。这通过调节胰腺酶泄漏减少炎症并抑制腺泡细胞凋亡，从而对TP产生治疗作用。
