Effect of microRNA‐27a‐5p on apoptosis and inflammatory response of pancreatic acinar cells in acute pancreatitis by targeting PTEN

Kong, Ling‐Bin; Wu, Qinghua; Zhao, Liangchao; Ye, Jinhua; Li, Nengping; Yang, Huali

doi:10.1002/jcb.28855

Cited by 25 publications

(16 citation statements)

References 22 publications

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“…Accumulating evidence demonstrates that cell apoptosis represents a favorable response during the course of SAP [11][12][13][14]. Apoptosis and necrosis, two forms of cell death, are key pathological responses of SAP.…”

Section: Introductionmentioning

confidence: 99%

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodiumtaurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP. Keywords APD • Severe acute pancreatitis • Apoptosis • PI3K/AKT signaling pathway Abbreviations AKT(PKB) Protein kinase B ANOVA One-way analysis of variance APD Abdominal paracentesis drainage Bcl-2 B-cell lymphoma 2 Caspase3 Cysteine aspartic acid protease 3 ELISA Enzyme-linked immunosorbent assay IL Interleukin MAP Mild acute pancreatitis MODS Multiple organ dysfunction syndrome NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells PAAF Pancreatitis associated ascitic fluids PI3K Phosphatidylinositide 3-kinases SAP Severe acute pancreatitis SIRS Systemic inflammatory response syndrome TNF-α TNF-α

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Section: Introductionmentioning

confidence: 99%

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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“…Thus, pancreatic ductal cells play critical roles in injury in AP. However, previous studies on AP have focused on pancreatic acinar cells (13)(14)(15), while studies on pancreatic ductal cells are limited (7).…”

Section: Introductionmentioning

confidence: 99%

Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway

Zhang

Guo

et al. 2019

Oncol Rep

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Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality rates. Pancreatic ductal cells are the most susceptible of all cell types that are exposed to the noxious stimuli of pancreatitis. Our previous studies demonstrated that emodin, a natural product extracted from Rheum palmatum L., protected pancreatic acinar cells from injutyh due to its anti-inflammatory activity. In the present study, in order to investigate the protective effects and molecular mechanisms of action of emodin on injured pancreatic ductal cells, an adenosine triphosphate (ATP)-induced model of cell injury was established using the human pancreatic ductal epithelial cell line, HPDE6-C7. The results revealed that emodin attenuated ATP-induced HPDE6-C7 cell injury by decreasing the levels of inflammatory factors, including interleukin (IL)-1β and IL-18. Furthermore, emodin significantly downregulated the protein levels of purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 in the injured HPDE6-C7 cells. The results also indicated that emodin attenuated HPDE6-C7 cell injury at least partially through the inhibition of the P2X7/NLRP3 signaling pathway. The protective effects of emodin were abrogated upon pre-treatment with P2X7 overexpression plasmid, which further confirmed that the P2X7 signaling pathway is the drug target of the effects of emodin against ATP-induced pancreatic ductal cell injury. Collectively, the findings of this study demonstrate that emodin attenuates ATP-induced pancreatic ductal cell injury in AP mainly through the inhibition of the P2X7/NLRP3 signaling pathway. This study suggests that emodin may be further developed for its application in future medical therapy.

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“…For instance, the deregulated miR-21 in NAFLD has been found to promote the pancreatic injury and inhibit necrotic acinar cell apoptosis in AP rats [12,13]. miR-27a not only regulated the hepatic lipid metabolism of NAFLD but also modulated the pancreatic acinar cell apoptosis and inflammation in AP [14,15]. miR-192-5p has been reported to regulate the lipid synthesis in NAFLD [16], but no information has been found for miR-192-5p in AP pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the occurrence of pancreatitis contributes to the severe pathological changes in pancreatic acinar cells, leading to the development of AP [28]. The damage in pancreatic acinar cells accelerates cell necrosis and leads to the release of enzymes and organelles to aggravate the inflammation of AP [15]. Thus, the cell apoptosis of pancreatic acinar cells is considered a self-protection strategy.…”

Section: Discussionmentioning

confidence: 99%

“…Some aberrantly expressed miRNAs have been found to be related with the occurrence and development of AP and NAFLD, providing candidate diagnostic biomarkers or therapeutic targets [10,11]. Among the functional miRNAs in NAFLD progression, several members have been found to be also involved in the development of AP, such as miR-21 [12,13] and miR-27a [14,15]. A study by Liu et al reported that microRNA-192-5p (miR-192-5p) was deregulated in NAFLD and involved in the regulation of lipid synthesis [16].…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of miR-192-5p in acute pancreatitis patients with nonalcoholic fatty liver and its functional role in acute pancreatitis progression

2020

Bioscience Reports

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Background: Nonalcoholic fatty liver disease (NAFLD) is a frequent metabolic disease and has been demonstrated to contribute to the severity of acute pancreatitis (AP). The present study aimed to investigate the aberrant expression of microRNA-192-5p (miR-192-5p) in AP patients with NAFLD, and further analyze the clinical significance and biological function of miR-192-5p in AP progression. Methods: Expression of miR-192-5p was estimated using quantitative real-time PCR (qRT-PCR). Diagnostic value of miR-192-5p was evaluated by the receiver operating characteristic curve (ROC). The effects of miR-192-5p on cell proliferation, apoptosis and inflammatory response of pancreatic acinar cells were further assessed by CCK-8 assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA). Results: Circulating miR-192-5p was decreased in AP patients with NAFLD compared with those patients without NAFLD and healthy controls (P<0.05). The down-regulated expression of miR-192-5p had a relative high diagnostic accuracy to distinguish the AP patients with NAFLD from the cases without NAFLD. Furthermore, the overexpression of miR-192-5p in pancreatic acinar cells led to the decreased cell proliferation, increased cell apoptosis and suppressed inflammatory reaction (all P<0.05). Conclusion: Collectively, all data indicated that serum expression of miR-192-5p in AP patients with NAFLD is significantly decreased and serves as a candidate diagnostic biomarker. The up-regulation of miR-192-5p in pancreatic acinar cell leads to increased cell apoptosis and decreased inflammatory response, suggesting the potential of miR-192-5p as a therapeutic target of AP.

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Effect of microRNA‐27a‐5p on apoptosis and inflammatory response of pancreatic acinar cells in acute pancreatitis by targeting PTEN

Cited by 25 publications

References 22 publications

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway

Dysregulation of miR-192-5p in acute pancreatitis patients with nonalcoholic fatty liver and its functional role in acute pancreatitis progression

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