机构：[1]Division of Hepatobiliopancreatic Surgery, Department of General Surgery,Nanfang Hospital, Southern Medical University, Guangzhou, China[2]Department of the Electronic Microscope Room, Central Laboratory, SouthernMedical University, Guangzhou, China[3]School of Traditional ChineseMedicine, Southern Medical University, Guangzhou, China[4]Department ofPathophysiology, Southern Medical University, Guangzhou, China[5]Department of Occupational Health and Medicine, Guangdong Provincial KeyLaboratory of Tropical Disease Research, School of Public Health, SouthernMedical University, Guangzhou, China[6]The First Clinical Medical College,Southern Medical University, Guangzhou, China[7]Laboratory Animal ResearchCenter of Nanfang Hospital, Southern Medical University, Guangzhou, China[8]Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science andBrain-Inspired Intelligence, Southern Medical University, Guangzhou, China[9]Department of Laboratory Medicine, Nanfang Hospital, Southern MedicalUniversity, Guangzhou, China[10]Department of Respiratory and Crit CareMedicine, Nanfang Hospital, Southern Medical University, Guangzhou, China[11]Department of Gynaecology and Obstetrics, Nanfang Hospital, SouthernMedical University, Guangzhou, China
Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.
基金：
The article is
supported by Guangdong Science and Technology Planning Project
(2019A030317018) & Scientific Research Startup Program of Southern Medical
University by High-level University Construction Funding of Guangdong
Provincial Department of Education (CX2018N012) & Clinical Research Program
of Nanfang Hospital, Southern Medical University (2018CR046) & College
Students’ Innovative Entrepreneurial Training Plan Program (201812121128,
201812121263) & Clinical Research Startup Program of Southern Medical
University by High-level University Construction Funding of Guangdong
Provincial Department of Education (LC2016PY011) & National Natural Science
Foundation of China (81801487).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区生物
小类|2 区细胞生物学
最新[2025]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Division of Hepatobiliopancreatic Surgery, Department of General Surgery,Nanfang Hospital, Southern Medical University, Guangzhou, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Tan Jie-Hui,Cao Rong-Chang,Zhou Lei,et al.EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis.[J].Cell death & disease.2020,11(11):966.doi:10.1038/s41419-020-03177-3.
APA：
Tan Jie-Hui,Cao Rong-Chang,Zhou Lei,Zhou Zhi-Tao,Chen Huo-Ji...&Zhang Guo-Wei.(2020).EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis..Cell death & disease,11,(11)
MLA：
Tan Jie-Hui,et al."EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis.".Cell death & disease 11..11(2020):966
生物学