Nonalcoholic Fatty Liver Hepatocyte-Derived lncRNA MALAT1 Aggravates Pancreatic Cell Inflammation via the Inhibition of Autophagy by Upregulating YAP

Abstract

Background. 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. Methods. The NAFLD cell model was constructed by treating HepG2 cells with FFA. The in vitro 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-α 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. Results. MALAT1 was upregulated in NAFLD-derived exosomes and increased the levels of IL-6 and TNF-α in pancreatic cells. NAFLD-derived exosomes inhibited YAP phosphorylation, decreased the levels of IL-6 and TNF-α, 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-α levels induced by MALAT1 in the AP cell model. Conclusions. NAFLD-derived MALAT1 exacerbates pancreatic cell inflammation via inhibiting autophagy by upregulating YAP.

Role of lncRNAs in acute pancreatitis: pathogenesis, diagnosis, and therapy

“…Mechanistically, the exosome-derived lncRNA MALAT1 was upregulated significantly and inhibited the hippo-YAP pathway and autophagy in AP. The YAP1 inhibitor CA3 could increase the LC3II/LC3I expression and reduce IL-6 and TNF-α levels induced by lncRNA MALAT1, suggesting that lncRNA MALAT1 aggravated AP by suppressing autophagy via the YAP pathway ( Liu D. et al, 2022 ). However, the specific mechanism of the YAP pathway to regulate autophagy in AP is unclear.…”

Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

“…Risk factors for AP include the presence of non-alcoholic fatty liver disease. The authors hypothesized that hepatocyte injury and the subsequent release of exosomes would foster the progression of AP [ 45 ]. Exosome-specific MALAT1 was secreted by damaged hepatocytes, which exacerbated inflammation in acinar cells by downregulating autophagy and upregulating the Hippo–YAP pathway [ 45 ].…”

Retracted: Nonalcoholic Fatty Liver Hepatocyte‐Derived lncRNA MALAT1 Aggravates Pancreatic Cell Inflammation via the Inhibition of Autophagy by Upregulating YAP

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”