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St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

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机构： [1]Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China. [2]Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [3]Department of the Electronic Microscope Room, Central Laboratory, Southern Medical University, Guangzhou 510515, China. [4]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. [5]Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China. [6]Department of Occupational Health and Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. [7]The First Clinical Medical College, Southern Medical University, Guangzhou 510515, China [8]Laboratory Animal Research Center of Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. [9]Guangdong‑Hong Kong‑Macao Greater Bay Area Center for Brain Science and Brain‑Inspired Intelligence, Southern Medical University, Guangzhou 510515, China. [10]Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. [11]Department of Respiratory and Crit Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. [12]Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. [13]Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangdong Institute, Guangzhou 510515, China. [14]Department of Plastic Surgery, The First Teaching Hospital, Xinjiang Medical University, Urumqi 830054, China.

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Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP.Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model.The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling.St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.© 2022. The Author(s).

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大类 | 2 区医学

小类 | 2 区医学：研究与实验

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大类 | 2 区

医学

小类 | 2 区医学：研究与实验

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第一作者机构： [1]Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China.

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