Emodin inhibits the progression of acute pancreatitis via regulation of lncRNA TUG1 and exosomal lncRNA TUG1

Yao

Computational Intelligence and Neuroscience

et al. 2022

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.

Section: Introductionmentioning

confidence: 99%

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

Yao

Computational Intelligence and Neuroscience

et al. 2022

Computational and Mathematical Methods in Medicine

“…Acute pancreatitis (AP) is one of the most frequent gastrointestinal diseases and has no specific treatment. It has been shown that dysfunction of pancreatic acinar cells can lead to AP progression [2]. In AP, gut barrier injury resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndromes.…”

Section: Introductionmentioning

confidence: 99%

Ibuprofen Alleviates Acute Pancreatitis– (AP–) Induced Myocardial Injury by Inhibiting AIM2

Chen

Wang

2022

Objective.The lack of certain trace elements such as selenium, molybdenum, magnesium or related nutrients in the soil, water quality and food in the disease area, which caused disturbance of myocardium metabolism and resulted in injury and necrosis. The aim of the study was to explore the mechanism of ibuprofen alleviating myocardial injury caused by acute pancreatitis (AP). Method. We have established AP cell model and rat model. HE staining is used for histological examination. ELISA is used to determine the levels of proinflammatory cytokines (TNF-α and IL-6) and markers of myocardial injury (LDH and CK-MB). qRT-PCR and Western blot are used to analyze the mRNA and protein levels of related genes. Results. The expression level of AIM2 was significantly increased in AP cells; downregulation of AIM2 alleviated inflammation and myocardial injury induced by AP cells; ibuprofen could inhibit the expression of AIM2 and alleviate inflammation and myocardial injury induced by AP cells. In vivo experiments have found that ibuprofen can inhibit the expression of AIM2 to alleviate myocardial injury in AP rat. Conclusion. Ibuprofen can alleviate myocardial injury caused by acute pancreatitis by inhibiting the expression of AIM2.

“…In contrast to ALI, TUG1 and exosomal TUG1 expression was stimulated to be upregulated in AR42J cells and was significantly associated with Treg cell differentiation. The overexpression of TUG1 promotes LPS/cerulein-induced apoptosis and inflammation in AR42J cells [ 52 ]. According to recent research, lncRNA TUG1 may play opposing roles in AP and ALI.…”

Section: Exosome-specific Ncrnasmentioning

confidence: 99%

“…Several in vivo and in vitro studies demonstrated emodin’s protective properties against AP-induced pancreatic injury, intestinal barrier dysfunction, and ALI [ 23 , 167 ]. Emodin was discovered to boost the differentiation and anti-inflammatory activity of regulatory T cells by stimulating the release of exosome-specific lncRNA taurine upregulated 1 (TUG1) from pancreatic acinar cells, hence limiting the development of AP [ 52 ]. Recent research suggests that the inflamed pancreas may release exosomes into the circulation during SAP.…”

Section: The Therapeutic Potential Of Exosomes In Ap and Associated Alimentioning

confidence: 99%

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

et al. 2022

Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients’ health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30–150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.