Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.

急性胰腺炎（AP）是一种炎症性、复杂的胰腺疾病，具有显着的发病率和死亡率。然而，AP发病机制涉及的分子和细胞机制仍有待阐明。在这里，我们探讨了 FOXF1 邻近非编码发育调节 RNA (FENDRR) 在 AP 进展中的作用。分别采用有或没有 LPS 诱导或牛磺石胆酸 3-硫酸 (TLC-S) 诱导的 AP 小鼠模型和细胞模型来验证 FENDRR 的体内和体外表达。对胰腺组织进行组织病理学检查以评估AP的严重程度。利用透射电子显微镜观察自噬液泡。进一步应用特异性靶向FENDRR的siRNA。采用流式细胞术评估细胞凋亡。还进行了 ELISA、免疫荧光和蛋白质印迹分析以确定炎症细胞因子和自噬活性的水平。进行 RNA 免疫沉淀 (RIP) 和染色质免疫沉淀 (ChIP) 测定，以揭示 FENDRR 对 ATG7 的表观遗传调控。此外，沉默 FENDRR 也在 AP 小鼠模型中得到验证。 AP 小鼠模型和细胞模型均显示较高的 FENDRR 和受损的自噬。 FENDRR 敲低可显着减弱雨蛙素或 TLC-S 诱导的 AR42J 细胞凋亡和自噬抑制。进一步的机制实验表明，FENDRR 的作用在一定程度上可归因于其通过与表观遗传阻遏物 PRC2 的直接相互作用来抑制 ATG7。此外，FENDRR的沉默显着诱导ATG7的促进，从而减轻体内AP的发展。 我们的研究强调 FENDRR 是一个可能促进 AP 进展的新靶点，为 AP 治疗提出了一个治疗靶点。