Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
General Surgery Center, General Hospital of Western Theater Command, Chengdu, Sichuan Province, China.
J Cell Mol Med. 2024 Feb;28(4):e18120. doi: 10.1111/jcmm.18120.
Our previous study confirmed that umbilical cord mesenchymal stem cells-exosomes (ucMSC-Ex) inhibit apoptosis of pancreatic acinar cells to exert protective effects. However, the relationship between apoptosis and autophagy in traumatic pancreatitis (TP) has rarely been reported. We dissected the transcriptomics after pancreatic trauma and ucMSC-Ex therapy by high-throughput sequencing. Additionally, we used rapamycin and MHY1485 to regulate mTOR. HE, inflammatory factors and pancreatic enzymatic assays were used to comprehensively determine the local versus systemic injury level, fluorescence staining and electron microscopy were used to detect the effect of autophagy, and observe the expression levels of autophagy-related markers at the gene and protein levels. High-throughput sequencing identified that autophagy played a crucial role in the pathophysiological process of TP and ucMSC-Ex therapy. The results of electron microscopy, immunofluorescence staining, polymerase chain reaction and western blot suggested that therapeutic effect of ucMSC-Ex was mediated by activation of autophagy in pancreatic acinar cells through inhibition of mTOR. ucMSC-Ex can attenuate pancreas injury by inhibiting mTOR to regulate acinar cell autophagy after TP. Future studies will build on the comprehensive sequencing of RNA carried by ucMSC-Ex to predict and verify specific non-coding RNA.
我们之前的研究证实，脐带间充质干细胞外泌体（ucMSC-Ex）通过抑制胰腺腺泡细胞凋亡发挥保护作用。然而，创伤性胰腺炎（TP）中凋亡和自噬之间的关系很少有报道。我们通过高通量测序分析了胰腺创伤和 ucMSC-Ex 治疗后的转录组学。此外，我们使用雷帕霉素和 MHY1485 来调节 mTOR。使用 HE 染色、炎症因子和胰腺酶测定来全面确定局部和全身损伤水平，荧光染色和电子显微镜观察自噬的效果，并观察自噬相关标志物在基因和蛋白水平上的表达水平。高通量测序结果表明，自噬在 TP 的病理生理过程中起着关键作用，ucMSC-Ex 治疗也发挥了作用。电子显微镜、免疫荧光染色、聚合酶链反应和 Western blot 的结果表明，ucMSC-Ex 通过抑制 mTOR 激活胰腺腺泡细胞自噬发挥治疗作用。ucMSC-Ex 可以通过抑制 mTOR 调节胰腺腺泡细胞自噬来减轻 TP 后的胰腺损伤。未来的研究将基于 ucMSC-Ex 携带的 RNA 的全面测序来预测和验证特定的非编码 RNA。
