PMID- 35463981 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20240225 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2022 DP - 2022 TI - Effects of Lipolysis-Stimulated Lipoprotein Receptor on Tight Junctions of Pancreatic Ductal Epithelial Cells in Hypertriglyceridemic Acute Pancreatitis. PG - 4234186 LID - 10.1155/2022/4234186 [doi] LID - 4234186 AB - OBJECTIVE: We investigated the effects of lipolysis-stimulated lipoprotein receptor (LSR) on the tight junctions (TJs) of pancreatic ductal epithelial cells (PDECs) in hypertriglyceridemic acute pancreatitis (HTGAP). METHODS: Sprague-Dawley rats were fed standard rat chow or a high-fat diet and injected with sodium taurocholate to obtain normal and HTGAP rats, respectively. Serum triglyceride (TG) levels, pathological changes, TJ proteins in the pancreas, and TJ ultrastructure of PDECs were assessed. LSR overexpression (OE) and knockdown (KD) HPDE6-C7 models were designed and cultured in a high-fat environment. Protein levels were quantified by Western blotting. Cell monolayer permeability was detected using FITC-Dextran. RESULTS: Serum TG concentration and pancreatic scores were higher in the HTGAP group than in the normal group. Among the TJ proteins, LSR protein expression was significantly lower in the HTGAP group than in the acute pancreatitis (AP) group. Tricellulin (TRIC) expression in the pancreatic ductal epithelia was higher in the HTGAP group than in the AP group. The HTGAP group had lower TJ protein levels, wider intercellular space, and widespread cellular necrosis with disappearance of cell junction structures. In the cell study, TJ proteins were downregulated and the cellular barrier was impaired by palmitic acid (PA), which was reversed by LSR-OE, whereas LSR-KD downregulated the TJ proteins and aggravated PA-induced cellular barrier impairment. CONCLUSIONS: Hypertriglyceridemia downregulates the TJ proteins in PDECs, which may impair the pancreatic ductal mucosal barrier function. LSR regulation can change the effects of HTG on cellular barrier function by upregulating the TJ proteins. CI - Copyright (c) 2022 Jie Wang et al. FAU - Wang, Jie AU - Wang J AUID- ORCID: 0000-0002-0106-7843 AD - Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Qin, Mengbin AU - Qin M AUID- ORCID: 0000-0001-9927-5482 AD - Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Wu, Qing AU - Wu Q AUID- ORCID: 0000-0002-8252-2990 AD - Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Yang, Huiying AU - Yang H AUID- ORCID: 0000-0002-2185-780X AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Wei, Biwei AU - Wei B AUID- ORCID: 0000-0002-8014-3911 AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Xie, Jinlian AU - Xie J AUID- ORCID: 0000-0003-1936-371X AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Qin, Yingying AU - Qin Y AUID- ORCID: 0000-0002-5496-0854 AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Liang, Zhihai AU - Liang Z AUID- ORCID: 0000-0001-5348-0130 AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Huang, Jiean AU - Huang J AUID- ORCID: 0000-0003-0431-1888 AD - Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China. LA - eng PT - Journal Article DEP - 20220414 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Lsr protein, rat) RN - 0 (Receptors, LDL) RN - 0 (Receptors, Lipoprotein) RN - 0 (Transcription Factors) SB - IM MH - Acute Disease MH - Animals MH - Epithelial Cells/metabolism/pathology MH - Hypertriglyceridemia/complications/metabolism MH - Lipolysis MH - *Pancreatitis/etiology/genetics/metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, LDL/genetics/metabolism MH - *Receptors, Lipoprotein/genetics/metabolism MH - Tight Junctions/metabolism MH - Transcription Factors/genetics/metabolism PMC - PMC9023160 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/04/26 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/04/14 CRDT- 2022/04/25 05:26 PHST- 2021/11/04 00:00 [received] PHST- 2022/03/17 00:00 [revised] PHST- 2022/04/04 00:00 [accepted] PHST- 2022/04/25 05:26 [entrez] PHST- 2022/04/26 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/14 00:00 [pmc-release] AID - 10.1155/2022/4234186 [doi] PST - epublish SO - Biomed Res Int. 2022 Apr 14;2022:4234186. doi: 10.1155/2022/4234186. eCollection 2022.