慢性胰腺炎患者接受全胰腺切除术并自体胰岛移植时循环 miRNA 的临床和生物学意义。
Clinical and biological significance of circulating miRNAs in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation.
发表日期:2023 Oct
作者:
Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin
来源:
Clinical and Translational Medicine
摘要:
慢性胰腺炎(CP)患者在全胰腺切除术(TPIAT)后胰岛输注期间,特定的 microRNA(miRNA)升高。我们的目的是识别胰腺损伤的循环 miRNA 特征,预测 miRNA-mRNA 网络,以确定与 CP 发病机制的潜在联系,并识别胰岛分离和移植功能结果。进行小 RNA 测序以识别 CP 中不同的循环 miRNA 特征。使用 miRCURY LNA SYBR green 定量实时聚合酶链反应测定法测量血浆 miRNA。使用R软件进行相关分析。使用 miRNet 和 miRNA 富集和注释工具确定 miRNA 靶点和疾病相互作用。与健康对照相比,脑瘫患者的循环 miRNA 发生了变化。对富含胰腺、其他组织和其他疾病(包括癌症和纤维化)的 12 种循环 miRNA 进行了进一步研究。胰腺中大约 2888 个 mRNA 是它们的目标,证明了与 76 个小分子的相互作用。三种 miRNA 表现出与吗啡的相互作用,五种表现出与葡萄糖的相互作用。 miRNA panel 针对与胰腺炎相关的 22 个基因。胰岛特异性、腺泡细胞特异性和肝脏特异性 miRNA 在胰岛输注后 6 小时升高,并在 TPIAT 后 3 个月恢复到基线水平。移植后 1 年,循环中的 miRNA 水平恢复至移植前水平。胰岛输注前和胰岛输注后 6 小时测量的循环 miRNA 与移植后 3 个月和 6 个月的代谢结果直接或负相关。miRNA 可能有助于 CP 发病机制,循环水平升高可能是胰腺炎症和纤维化所特有的,值得进一步研究.© 2023 作者。约翰·威利出版的《临床与转化医学》
Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant.miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.