Role of Sp1 and NCX1 in the development of acute pancreatitis induced by caerulein

Wanling LI; Jingjing LIU; Yuyang CHEN; Hui DONG; Bingqiang ZHANG

doi:10.16016/j.1000-5404.201810152

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Role of Sp1 and NCX1 in the development of acute pancreatitis induced by caerulein

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- Role of Sp1 and NCX1 in the development of acute pancreatitis induced by caerulein
- Journal of Third Military Medical University Vol. 41, Issue 8, Pages: 757-762(2019)
- 作者机构：
  
  1..400016 重庆，重庆医科大学附属第一医院消化内科Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016
  2..400037 重庆，陆军军医大学(第三军医大学)第二附属医院消化内科Department of Gastroenterology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81400667);the General Project of Basic Science and Frontier Technology Research of Chongqing(CSTC2016JCYJA0017)
- DOI：10.16016/j.1000-5404.201810152
  CLC： R394.2;R363.21;R576
- Received：24 October 2018，
  
  Published：30 April 2019
- 稿件说明：
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Wanling LI, Jingjing LIU, Yuyang CHEN, et al. Role of Sp1 and NCX1 in the development of acute pancreatitis induced by caerulein[J]. Journal of Third Military Medical University, 2019, 41(8): 757-762.
DOI：

Wanling LI, Jingjing LIU, Yuyang CHEN, et al. Role of Sp1 and NCX1 in the development of acute pancreatitis induced by caerulein[J]. Journal of Third Military Medical University, 2019, 41(8): 757-762. DOI： 10.16016/j.1000-5404.201810152.

摘要

目的

观察雨蛙素刺激对胰腺外分泌细胞增殖、自噬的影响，探讨Sp1/NCX1通路在急性胰腺炎(acute pancreatitis，AP)中的作用及其机制。

方法

雨蛙素刺激胰腺腺泡细胞AR42J，体外诱导急性胰腺炎细胞模型，采用CCK-8检测雨蛙素处理后不同时间(0、24、48、72 h)的细胞增殖情况。Western blot检测自噬的经典标记物LC3Ⅰ和LC3Ⅱ在雨蛙素处理后不同时间(3、6、12、24 h)的表达变化。采用qRT-PCR、Western blot分别检测雨蛙素处理不同时间(1、3、6、12、24 h)Sp1 mRNA及蛋白水平的表达变化。应用免疫组化染色技术观察雨蛙素构建的大鼠AP模型中Sp1的表达情况。Western blot检测Sp1抑制剂Mithramycin A处理AR42J细胞后NCX1蛋白水平变化。

结果

雨蛙素可抑制AR42J细胞的增殖(

0.05)，并使LC3Ⅱ/LC3Ⅰ比值增加。雨蛙素还可上调AR42J细胞中转录因子Sp1的mRNA和蛋白表达(

0.05)；雨蛙素腹腔注射可导致大鼠胰腺组织中Sp1蛋白表达上调，而在AR42J细胞中抑制Sp1蛋白可抑制钠钙交换体NCX1蛋白的表达。

结论

Sp1上调NCX1的表达在雨蛙素诱导的急性胰腺炎中发挥促进作用。

Abstract

Objective

To explore the pathogenic roles of Sp1/NCX1 pathway in acute pancreatitis (AP) induced by caerulein.

Methods

Pancreatic acinar AR42J cells were stimulated with caerulein to establish a cell model of AP. CCK8 assay was used to evaluate the cell proliferation at 0

48 and 72 h after caerulein treatment

and the expression of LC3Ⅱ/LC3Ⅰ

the classic autophagy markers

were detected using Western blotting at 3

and 24 h after the treatment. qRT-PCR and Western blotting were used to detect the cellular expression of Sp1 at both the mRNA and protein levels at 1

and 24 h. In a rat model of caerulein-induced AP

immunohistochemistry was used to observe the expression of Sp1 in the pancreas. The effect of Mithramycin A

an inhibitor of Sp1

on the expression of NCX1 protein in AR42J cells was tested using Western blotting.

Results

Caerulein significantly inhibited the proliferation and promoted the ratio of LC3Ⅱ/LC3Ⅰ in AR42J cells. Caerulein also significantly enhanced the mRNA and protein levels of Sp1 in AR42J cells (

0.05). Immunohistochemical staining showed that intraperitoneal injection of cearulein obviously up-regulated the expression level of Sp1 protein in the pancreas of rats. In AR42J cells

inhibition of Sp1 expression with Mithramycin A significantly suppressed the expression of NCX1 protein.

Conclusion

Sp1 plays a facilitating role in the development of caerulein-induced AP by up-regulating the expression of NCX1.

关键词

Keywords

references

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