Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis

Tang, Xiping; Tang, Guodu; Liang, Zhihai; Qin, Mengbin; Fang, Chunyun; Zhang, Luyi

doi:10.1097/mpa.0000000000000946

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…It has been reported that pancreatitis increased the accumulation of inflammatory cells and mediators, promoting the deterioration of pancreatitis. 6 Recent research revealed that occurrence of pancreatitis, resulting in severe pathological changes in pancreatic acinar cells, plays an important role in the occurrence and development of pancreatitis. 7 When the pancreatic acinar cells were damaged, the number of cells necrosis increased and a variety of enzymes and organelles in cells were released, and accompanied by acute inflammation, leading to acute severe pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

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

Kong

Zhao

et al. 2019

J of Cellular Biochemistry

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To investigate the apoptosis and inflammatory response of microRNA‐27a‐5p (miR‐27a‐5p) in pancreatic acinar cells of acute pancreatitis (AP) and its related mechanisms. Rat pancreatic acinar cell line AR42J was treated with caerulein (10nmol/L) to construct an acute pancreatitis cell model. Quantitative real‐time polymerase chain reaction was performed to measure the expression of miR‐27a‐5p; The miR‐27a‐5p mimic was transfected into cell, and the apoptosis rate of the cells was detected by flow cytometry; The levels of TNF‐α, IL‐1, and IL‐6 in the culture supernatant were determined by enzyme‐linked immunosorbent assay; TargetScans database predicted and dual luciferase reporter gene assay verified the relationship between miR‐27a‐5p and the phosphatase and tensin homolog deleted on chromosome 10 (PTEN); The recovery experiment explored the apoptosis and the effects of inflammatory responses. The expression of miR‐27a‐5p decreased gradually (P < 0.05) and the expression of PTEN increased gradually (P < 0.05) with the prolongation of acting time. Upregulation of miR‐27a‐5p significantly promoted cell apoptosis (P < 0.05) and inhibited inflammatory response (P < 0.05); The TargetScans database predicted that the 3'UTR of PTEN contains a base complementary to the miR‐27a‐5p seed region. Cotransfection of wild‐type vector (PTEN‐WT) with miR‐27a‐5p mimic or miR‐27a‐5p inhibitor significantly affected the relative activity of luciferase (P < 0.05), and no significant impact was observed in mutant PTEN‐MUT. Compared with miR‐27a‐5p + pcDNA group, transfection of miR‐27a‐5p mimic and pcDNA‐PTEN significantly increased the expression of PTEN (P < 0.05), decreased the apoptotic rate (P < 0.05), and increased the inflammatory response (P < 0.05). miR‐27a‐5p induced apoptosis and inhibited the inflammatory response of pancreatic acinar cells in AP by targeting PTEN.

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Section: Discussionmentioning

confidence: 99%

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

Kong

Zhao

et al. 2019

J of Cellular Biochemistry

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“…AR42J cells are an immortalized rat pancreatic cell line that share similarities with acinar cells, including synthesis and secretion of digestive enzymes, as well as receptor expression and signal transduction mechanisms [5,6]. Therefore, AR42J cells demonstrate an appropriate invitro model for the study of the function of the exocrine pancreas and experimental AP induced by CN [7][8][9][10][11][12]. However, as indicated by Table 1, the conditions and used protocols for the analysis of CN-induced pancreatitis in AR42J remain heterogeneous and are, at least in part, contradictory.…”

Section: Discussionmentioning

confidence: 99%

“…They maintain the characteristics of normal pancreatic acinar cells including calcium signaling, the synthesis and secretion of digestive enzymes, receptor expression and signal transduction mechanisms [5,6]. Thus, AR42J cells have been widely used to study the function of the exocrine pancreas and as an in-vitro model of CN-induced AP [7][8][9][10][11][12]. However, during the process of immortalization and premalignant transformation, this cell line also exhibits an amphicrine potential that is indicated by neuroendocrine properties, hormone production (mainly gastrin) and autocrine stimulation [13].…”

Section: Introductionmentioning

confidence: 99%

Pitfalls in AR42J-model of cerulein-induced acute pancreatitis

et al. 2021

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Background AR42J are immortalized pancreatic adenocarcinoma cells that share similarities with pancreatic acinar cells. AR42J are often used as a cell-culture model of cerulein (CN)-induced acute pancreatitis (AP). Nevertheless, it is controversial how to treat AR42J for reliable induction of AP-like processes. Gene knockout and/or overexpression often remain challenging, as well. In this study, we demonstrate conditions for a reliable induction of proinflammatory markers upon CN treatment in AR42J and high transfection efficacy using Glyoxalase-I (Glo-I) as a target of interest. Methods Effects of dexamethasone (dexa) and CN on cell morphology and amylase secretion were analyzed via ELISA of supernatant. IL-6, TNF-α and NF-κB-p65 were measured via qRT-PCR, ELISA and Western Blot (WB). Transfection efficacy was determined by WB, qRT-PCR and immune fluorescence of pEGFP-N1-Glo-I-Vector and Glo-I-siRNA. Results Treatment of AR42J with 100 nm dexa is mandatory for differentiation to an acinar-cell-like phenotype and amylase production. CN resulted in secretion of amylase but did not influence amylase production. High levels of CN-induced amylase secretion were detected between 3 and 24 hours of incubation. Treatment with LPS alone or in combination with CN did not influence amylase release compared to control or CN. CN treatment resulted in increased TNF-α production but not secretion and did not influence IL-6 mRNA. CN-induced stimulation of NF-κB was found to be highest on protein levels after 6h of incubation. Transient transfection was able to induce overexpression on protein and mRNA levels, with highest effect after 12 to 24 hours. Gene-knockdown was achieved by using 30 pmol of siRNA leading to effective reduction of protein levels after 72 hours. CN did not induce amylase secretion in AR42J cell passages beyond 35. Conclusion AR42J cells demonstrate a reliable in-vitro model of CN-induced AP but specific conditions are mandatory to obtain reproducible data.

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“…The protective effect of ghrelin was also found in cellular models of acute pancreatitis [ 121 , 122 , 123 ]. On the other hand, inhibition of ghrelin gene expression in pancreatic acinar cells, AR42J cells, results in increased expression of intracellular inflammatory factors after administration of cerulein [ 124 ].…”

Section: Protective Anti-inflammatory and Healing Effects Of Ghrelin In The Digestive Systemmentioning

confidence: 99%

Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System

Ginter

Ceranowicz

Warzecha

2021

IJMS

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Ghrelin is an endogenous ligand for the ghrelin receptor, previously known as the growth hormone secretagogue receptor. This hormone is mainly produced by endocrine cells present in the gastric mucosa. The ghrelin-producing cells are also present in other organs of the body, mainly in the digestive system, but in much smaller amount. Ghrelin exhibits a broad spectrum of physiological effects, such as stimulation of growth hormone secretion, gastric secretion, gastrointestinal motility, and food intake, as well as regulation of glucose homeostasis and bone formation, and inhibition of inflammatory processes. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut, and also presents the role of growth hormone and insulin-like growth factor-1 in these effects. In addition, the current data on the possible influence of ghrelin on the carcinogenesis, its importance in predicting the risk of developing gastrointestinal malignances, as well as the potential usefulness of ghrelin in the treatment of cancer, have been presented.

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Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis

Abstract: Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload.

Cited by 9 publications

References 26 publications

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

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

Pitfalls in AR42J-model of cerulein-induced acute pancreatitis

Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System

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