ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway

doi:10.1038/s41419-022-04657-4

	ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway
	Ji, Liang 1,2; Wang, Zhi-hong 3; Zhang, Yu-hua 4,5; Zhou, Yi 1,2; Tang, De-sheng 1,6; Yan, Chang-sheng 1,6; Ma, Jia-min 1,6; Fang, Kun 1,6; Gao, Lei 1,6; Ren, Nian-sheng 1,6
刊名	CELL DEATH & DISEASE
	2022-03-07
卷号	13
ISSN号	2041-4889
DOI	10.1038/s41419-022-04657-4
通讯作者	Wang, Gang(wgilu79@163.com)
英文摘要	The present study was performed to explore whether and how impaired autophagy could modulate calcium/calmodulin-dependent protein kinase II (CAMKII)-regulated necrosis in the pathogenesis of acute pancreatitis (AP). Wistar rats and AR42J cells were used for AP modeling. When indicated, genetic regulation of CAMKII or ATG7 was performed prior to AP induction. AP-related necrotic injury was positively regulated by the incubation level of CAMKII. ATG7 positively modulated the level of CAMKII and necrosis following AP induction, indicating that there might be a connection between impaired autophagy and CAMKII-regulated necrosis in the pathogenesis of AP. microRNA (miR)-30b-5p was predicted and then verified as the upstream regulator of CAMKII mRNA in our setting of AP. Given that the level of miR-30b-5p was negatively correlated with the incubation levels of ATG7 after AP induction, a rescue experiment was performed and indicated that the miR-30b-5p mimic compromised ATG7 overexpression-induced upregulation of CAMKII-regulated necrosis after AP induction. In conclusion, our results indicate that ATG7-enhanced impaired autophagy exacerbates AP by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.
资助项目	National Natural Science Foundation of China[81770639] ; National Natural Science Foundation of China[82070657] ; National Natural Science Foundation of China[81900586] ; Application Technology Research and Development Project of Heilongjiang Province[GA20C019] ; First Affiliated Hospital of Harbin Medical University Fund for Distinguished Young Scholars[HYD2020JQ0006] ; First Affiliated Hospital of Harbin Medical University Fund for Distinguished Young Scholars[HYD2020JQ0010] ; Chinese Research Hospital Association[Y2019FH-DTCC-SB1] ; Innovative Research Funds of the First Affiliated Hospital of Harbin Medical University[2018BS013] ; Postdoctoral Fund of Heilongjiang Province[LBH-Z18131]
WOS关键词	MITOCHONDRIAL PERMEABILITY TRANSITION ; MIXED LINEAGE KINASE ; STRESS ; RIP3 ; PORE
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000765801600002
资助机构	National Natural Science Foundation of China ; Application Technology Research and Development Project of Heilongjiang Province ; First Affiliated Hospital of Harbin Medical University Fund for Distinguished Young Scholars ; Chinese Research Hospital Association ; Innovative Research Funds of the First Affiliated Hospital of Harbin Medical University ; Postdoctoral Fund of Heilongjiang Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/128449]
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Gang
作者单位	1.Minist Educ, Key Lab Hepatosplen Surg, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China 2.Harbin Med Univ, Dept Breast Surg, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China 3.China Med Univ, Dept Thyroid Surg, Hosp 1, 155 Nanjing North St, Shenyang 110001, Liaoning, Peoples R China 4.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Hepatopancreatobiliary Surg, 1 Banshan Rd, Hangzhou 310022, Zhejiang, Peoples R China 5.Chinese Acad Sci, Inst Basic Med & Canc IBMC, 1 Banshan Rd, Hangzhou 310022, Zhejiang, Peoples R China 6.Harbin Med Univ, Dept Pancreat & Biliary Surg, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China
推荐引用方式 GB/T 7714	Ji, Liang,Wang, Zhi-hong,Zhang, Yu-hua,et al. ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway[J]. CELL DEATH & DISEASE,2022,13.
APA	Ji, Liang.,Wang, Zhi-hong.,Zhang, Yu-hua.,Zhou, Yi.,Tang, De-sheng.,...&Wang, Gang.(2022).ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.CELL DEATH & DISEASE,13.
MLA	Ji, Liang,et al."ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway".CELL DEATH & DISEASE 13(2022).