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EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis.
Tan, Jie-Hui; Cao, Rong-Chang; Zhou, Lei; Zhou, Zhi-Tao; Chen, Huo-Ji; Xu, Jia; Chen, Xue-Mei; Jin, Yang-Chen; Lin, Jia-Yu; Qi, Zhao-Chang; Zeng, Jun-Ling; Li, Shu-Ji; Luo, Min; Hu, Guo-Dong; Jin, Jin; Zhang, Guo-Wei.
Afiliación
  • Tan JH; Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Cao RC; Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Zhou L; Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Zhou ZT; Department of the Electronic Microscope Room, Central Laboratory, Southern Medical University, Guangzhou, China.
  • Chen HJ; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
  • Xu J; Department of Pathophysiology, Southern Medical University, Guangzhou, China.
  • Chen XM; Department of Occupational Health and Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • Jin YC; The First Clinical Medical College, Southern Medical University, Guangzhou, China.
  • Lin JY; The First Clinical Medical College, Southern Medical University, Guangzhou, China.
  • Qi ZC; The First Clinical Medical College, Southern Medical University, Guangzhou, China.
  • Zeng JL; Laboratory Animal Research Center of Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Li SJ; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China.
  • Luo M; Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Hu GD; Department of Respiratory and Crit Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Jin J; Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Zhang GW; Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. guoweizhang77@163.com.
Cell Death Dis ; 11(11): 966, 2020 11 11.
Article en En | MEDLINE | ID: mdl-33177505
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis Crónica / Factor Apoptótico 1 Activador de Proteasas / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Middle aged Idioma: En Revista: Cell Death Dis Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis Crónica / Factor Apoptótico 1 Activador de Proteasas / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Middle aged Idioma: En Revista: Cell Death Dis Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido