Department of General Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, 241001, China.
Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
Sci Rep. 2017 Apr 3;7(1):581. doi: 10.1038/s41598-017-00629-3.
Acute pancreatitis (AP) is a common acute abdominal disease, 10-20% of which can evolve into severe AP (SAP) causing significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential of repairing SAP, but the detailed mechanism remains unknown. We demonstrate here that microRNA-9 (miR-9) modified BMSCs (pri-miR-9-BMSCs) can significantly reduce the pancreatic edema, infiltration, hemorrhage, necrosis, the release of amylase and lipase. Meanwhile, decreased local/systemic inflammatory response (TNF-α↓, IL-1β↓, IL-6↓, HMGB1↓, MPO↓, CD68↓, IL-4↑, IL-10↑, and TGF-β↑) and enhanced regeneration of damaged pancreas (Reg4↑, PTF1↑, and PDX1↑) are also promoted. But these effects diminish or disappear after antagonizing miR-9 (TuD). Besides, we find that miR-9 is negatively correlated with AP and miR-9 agomir which can mimic the effects of pri-miR-9-BMSCs and protect injured pancreas. Furthermore, we investigate that BMSCs deliver miR-9 to the injured pancreas or peripheral blood mononuclear cell (PBMC), which can target the NF-κB1/p50 gene and inhibit the NF-κB signaling pathway (p-P65↓, NF-κB1/p50↓, IκBα↑, IκBβ↑). Taken together, these results show that miR-9 is a key paracrine factor of BMSCs attenuating SAP targeting the NF-κB1/p50 gene and suppressing the NF-κB signaling pathway.
急性胰腺炎（AP）是一种常见的急性腹部疾病，其中 10-20%可发展为严重的 AP（SAP），导致显著的发病率和死亡率。骨髓间充质干细胞（BMSCs）具有修复 SAP 的潜力，但详细机制尚不清楚。我们在此证明，微小 RNA-9（miR-9）修饰的 BMSCs（pri-miR-9-BMSCs）可显著减轻胰腺水肿、浸润、出血、坏死、淀粉酶和脂肪酶的释放。同时，降低局部/全身炎症反应（TNF-α↓，IL-1β↓，IL-6↓，HMGB1↓，MPO↓，CD68↓，IL-4↑，IL-10↑，和 TGF-β↑）和增强受损胰腺的再生（Reg4↑，PTF1↑，和 PDX1↑）也得到促进。但是，这些作用在拮抗 miR-9（TuD）后会减少或消失。此外，我们发现 miR-9 与 AP 呈负相关，miR-9 激动剂可模拟 pri-miR-9-BMSCs 的作用并保护受损的胰腺。此外，我们研究了 BMSCs 将 miR-9 递送至受伤的胰腺或外周血单核细胞（PBMC），其可靶向 NF-κB1/p50 基因并抑制 NF-κB 信号通路（p-P65↓，NF-κB1/p50↓，IκBα↑，IκBβ↑）。总之，这些结果表明，miR-9 是 BMSCs 减轻 SAP 的关键旁分泌因子，其靶向 NF-κB1/p50 基因并抑制 NF-κB 信号通路。
