circZMYM2/miR-29a/PUMA轴对急性胰腺炎腺泡细胞凋亡的影响及作用机制

doi:10.7659/j.issn.1005-6947.2023.09.007

首页 > 按期查看>2023年第9期 >1341-1348. DOI:10.7659/j.issn.1005-6947.2023.09.007

circZMYM2/miR-29a/PUMA轴对急性胰腺炎腺泡细胞凋亡的影响及作用机制
DOI:
                        10.7659/j.issn.1005-6947.2023.09.007
                    
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作者单位:安徽医科大学第二附属医院 急诊外科，安徽 合肥 230601
作者简介:高明，安徽医科大学第二附属医院主任医师，主要从事急诊医学方面的研究。
通信作者:李贺，Email: lihe@ahmu.edu.cn
基金项目:安徽医科大学校科学研究基金资助项目（2020xkj192）。

Impact of the circZMYM2/miR-29a/PUMA axis on acinar cell apoptosis in acute pancreatitis and its action mechanism

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Department of Emergency Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China

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摘要:

背景与目的 腺泡细胞凋亡在急性胰腺炎（AP）炎症反应和病情进展中发挥重要作用，进一步了解腺泡细胞的凋亡机制及相关通路有助于为AP特异性治疗提供新思路。本研究探讨锌指蛋白基因ZMYM2转录环状核糖核酸（circZMYM2）、微小RNA-29a（miR-29a）与p53上调凋亡调节因子（PUMA）在AP中的表达及其之间的潜在关系。方法将大鼠胰腺腺泡细胞AR42J用雨蛙素诱导AP体外模型（AP组），或先通过pcDNA3.1-si-ZMYM2转染，敲低circZMYM2后再用雨蛙素诱导AP体外模型（si-circZMYM2组），以无处理的AR42J细胞作为对照组。3 h后分别用ELISA法检测细胞淀粉酶水平、CCK-8法检测细胞活力、流式细胞术与TUNEL法检测细胞凋亡情况、Western blot法检测细胞PUMA蛋白表达、qRT-PCR检测细胞circZMYM2与miR-29a表达。结果与对照组比较，AP组与si-circZMYM2组淀粉酶水平均明显升高、细胞活力均明显降低、细胞凋亡率或凋亡细胞数均明显增加、PUMA蛋白表达水平均明显升高，但si-circZMYM2组以上指标的变化程度均明显低于AP组（均P<0.05）。与对照组比较，circZMYM2表达水平在AP组明显升高，在si-circZMYM2组明显降低，而miR-29a表达水平在AP组明显降低，在si-circZMYM2组明显升高（均P<0.05）。结论 circZMYM2在AP的腺泡细胞中表达升高，其可能通过与miR-29a内源性竞争作用，抑制miR-29a的表达，从而上调PUMA表达水平，促进腺泡细胞凋亡和AP进展。

Abstract:

Background and Aims Apoptosis of acinar cells plays a crucial role in the inflammatory response and progression of acute pancreatitis (AP). A better understanding of the apoptotic mechanisms and related pathways in acinar cells can provide new insights for AP-specific therapies. This study was conducted to investigate the expressions of the zinc finger protein gene ZMYM2 transcribed circular RNA (circZMYM2), microRNA-29a (miR-29a), and p53 upregulated modulator of apoptosis (PUMA) in AP and their potential relationships.Methods Rat pancreatic acinar cells AR42J were induced to form an in vitro model of AP using cerulein (AP group) or were transfected with pcDNA3.1-si-ZMYM2 to knock down circZMYM2 expression before cerulein induction (si-circZMYM2 group), using untreated AR42J cells as a control group. After 3 h, the amylase level was determined by ELISA assay, the cell viability was assessed by CCK-8 assay, the apoptosis was measured by flow cytometry and TUNEL assay, and the PUMA protein expression was examined by Western blot analysis, and the circZMYM2 and miR-29a expression levels were detected by qRT-PCR method.Results Compared to the control group, the AP group and si-circZMYM2 group showed significantly increased amylase levels, decreased cell viability, increased apoptosis rates or apoptotic cell numbers, and elevated PUMA protein expression (all P<0.05). However, the changes in the above indicators were significantly less pronounced in the si-circZMYM2 group than those in the AP group (all P<0.05). The expression level of circZMYM2 was significantly increased in the AP group and significantly decreased in the si-circZMYM2 group, while the expression level of miR-29a was significantly downregulated in the AP group and significantly upregulated in the si-circZMYM2 group compared to the control group (all P<0.05).Conclusion The expression of circZMYM2 in acinar cells during AP is upregulated, and it may probably inhibit miR-29a expression through endogenous competition, thereby upregulate PUMA expression level and then promote acinar cell apoptosis and AP progression.