Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
Comput Intell Neurosci. 2022 Aug 31;2022:2930960. doi: 10.1155/2022/2930960. eCollection 2022.
Acute pancreatitis (AP) is one of the most common gastrointestinal disorders, which causes death with a high mortality rate of about 30%. The study aims to identify whether the nonalcoholic fatty liver disease (NAFLD)-derived lncRNA MALAT1 participates in the inflammation of pancreatic cell and its potential mechanism.
The NAFLD cell model was constructed by treating HepG2 cells with FFA. The model of acute pancreatitis (AP) was established by the administration of caerulein on AR42J cells. MALAT1 and si-MALAT1 were transfected into pancreatic cells, and then exosomes were collected from the NAFLD cell model and then were cocultured with AR42J cells. Transmission electron microscopy was used to observe the morphology of exosomes. Oil Red O staining was applied to reveal the lipid deposition. The triglyceride, IL-6, and TNF- levels were detected using ELISA. The MALAT1 level in exosomes was detected by qRT-PCR. The CD9, CD63, CD81, and CYP2E1, LC3II, and LC3I levels were detected by western blot.
MALAT1 was upregulated in NAFLD-derived exosomes and increased the levels of IL-6 and TNF- in pancreatic cells. NAFLD-derived exosomes inhibited YAP phosphorylation, decreased the levels of IL-6 and TNF-, and reduced the ratio of LC3II/LC3I protein in pancreatic cells. Silencing MALAT1 significantly returned the inhibitory effect of NAFLD on hippo-YAP pathway. YAP1 signal transduction inhibitor CA3 reversed the decrease of LC3II/LC3I expression and the increase of IL-6 and TNF- levels induced by MALAT1 in the AP cell model.
NAFLD-derived MALAT1 exacerbates pancreatic cell inflammation via inhibiting autophagy by upregulating YAP.
急性胰腺炎（AP）是最常见的胃肠道疾病之一，其死亡率约为 30%，导致死亡。本研究旨在确定非酒精性脂肪性肝病（NAFLD）衍生的长链非编码 RNA MALAT1 是否参与胰腺细胞的炎症及其潜在机制。
用游离脂肪酸（FFA）处理 HepG2 细胞构建 NAFLD 细胞模型。用蛙皮素（caerulein）处理 AR42J 细胞建立急性胰腺炎（AP）模型。将 MALAT1 和 si-MALAT1 转染到胰腺细胞中，然后从 NAFLD 细胞模型中收集外泌体，并与 AR42J 细胞共培养。透射电子显微镜用于观察外泌体的形态。油红 O 染色显示脂质沉积。ELISA 检测甘油三酯、IL-6 和 TNF-α水平。qRT-PCR 检测外泌体中的 MALAT1 水平。Western blot 检测 CD9、CD63、CD81 和 CYP2E1、LC3II 和 LC3I 水平。
MALAT1 在 NAFLD 衍生的外泌体中上调，并增加了胰腺细胞中 IL-6 和 TNF-α的水平。NAFLD 衍生的外泌体抑制 YAP 磷酸化，降低 IL-6 和 TNF-α水平，并降低胰腺细胞中 LC3II/LC3I 蛋白的比值。沉默 MALAT1 可显著恢复 NAFLD 对 hippo-YAP 通路的抑制作用。YAP1 信号转导抑制剂 CA3 逆转了 MALAT1 在 AP 细胞模型中诱导的 LC3II/LC3I 表达降低和 IL-6、TNF-α水平升高。
NAFLD 衍生的 MALAT1 通过上调 YAP 抑制自噬，加重胰腺细胞炎症。
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