Progress of Pancreatic Stellate Cells in Research of Pancreatic Disease Model

doi:10.12300/j.issn.1674-5817.2021.088

Abstract

Abstract:

Common types of pancreatic diseases are pancreatitis, diabetes and pancreatic cancer. Clinical studies have found that pancreatic stellate cells (PSCs) in patients with pancreatic diseases, contributes to fibrosis, oxidative stress and inflammation, and lead to pancreatic diseases. This article reviewed the modeling methods of different pancreatic diseases, and the influence and application prospects of PSCs in pancreatic diseases, providing a new idea for the research and treatment of pancreatic diseases.

Key words: Animal model, Pancreatic stellate cells, Pancreatic disease

CLC Number:

Q95-33

Xun WEI,Xia JIANG,Yuxuan ZHENG,et al. Progress of Pancreatic Stellate Cells in Research of Pancreatic Disease Model[J]. Laboratory Animal and Comparative Medicine, 2022, 42(2): 146-151. DOI: 10.12300/j.issn.1674-5817.2021.088.

References 45

1	凤振宁, 金世柱. 急性胰腺炎动物模型构建方法的研究[J]. 胃肠病学和肝病学杂志, 2020, 29(4):388-391. DOI:10.3969/j.issn. 1006-5709.2020.04.006 .
2	PANG T C Y, WILSON J S, APTE M V. Pancreatic stellate cells: what's new? [J]. Curr Opin Gastroenterol, 2017, 33(5):366-373. DOI:10.1097/MOG.0000000000000378 .
3	BYNIGERI R R, JAKKAMPUDI A, JANGALA R, et al. Pancreatic stellate cell: Pandora's box for pancreatic disease biology[J]. World J Gastroenterol, 2017, 23(3):382-405. DOI:10.3748/wjg.v23.i3.382 .
4	SHERMAN M H. Stellate cells in tissue repair, inflammation, and cancer[J]. Annu Rev Cell Dev Biol, 2018, 34:333-355. DOI:10.1146/annurev-cellbio-100617-062855 .
5	OMARY M B, LUGEA A, LOWE A W, et al. The pancreatic stellate cell: a star on the rise in pancreatic diseases[J]. J Clin Invest, 2007, 117(1):50-59. DOI: 10.1172/JCI30082 .
6	LI W, LIU H, QIAN W K, et al. Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer[J]. Comput Struct Biotechnol J, 2018, 16:479-487. DOI:10.1016/j.csbj.2018.10.006 .
7	HUANG Q, HUANG M, MENG F, et al. Activated pancreatic stellate cells inhibit NK cell function in the human pancreatic cancer microenvironment[J]. Cell Mol Immunol, 2019, 16(1):87-89. DOI:10.1038/s41423-018-0014-2 .
8	APTE M V, HABER P S, APPLEGATE T L, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture[J]. Gut, 1998, 43(1):128-133. DOI:10.1136/gut.43.1.128 .
9	许小凡, 吴楠, 朱林佳, 等. 昆明小鼠胰腺星状细胞分离培养与鉴定[J]. 新乡医学院学报, 2016, 33(7):564-567. DOI:10.7683/xxyxyxb.2016.07.004 .
10	MANDALIA A, WAMSTEKER E J, DIMAGNO M J. Recent advances in understanding and managing acute pancreatitis[J]. F1000Research, 2018, 7: F1000 Faculty Rev-F1000 Faculty 959. DOI:10.12688/f1000research.14244.2 .
11	杨晶晶, 张丹, 陈嘉屿. 急性胰腺炎动物模型研究进展[J]. 解放军医学杂志, 2019, 44(11):984-990. DOI:10.11855/j.issn.0577-7402.2019.11.16 .
12	张林燚, 白明, 苗明三. 基于中西医临床病证特点的急性胰腺炎动物模型分析[J]. 中国实验方剂学杂志, 2021, 27(12):196-201. DOI:10.13422/j.cnki.syfjx.20211104 .
13	HABTEZION A. Inflammation in acute and chronic pancreatitis[J]. Curr Opin Gastroenterol, 2015, 31(5):395-399. DOI:10.1097/MOG.0000000000000195 .
14	LIOU G Y, DÖPPLER H, NECELA B, et al. Macrophage-secreted cytokines drive pancreatic acinar-to-ductal Metaplasia through NF-κB and MMPs[J]. J Cell Biol, 2013, 202(3):563-577. DOI:10.1083/jcb.201301001 .
15	SEMWAL D K, KUMAR A, ASWAL S, et al. Protective and therapeutic effects of natural products against diabetes mellitus via regenerating pancreatic β-cells and restoring their dysfunction[J]. Phytother Res, 2021, 35(3):1218-1229. DOI:10.1002/ptr.6885 .
16	江霞, 钱豪杰, 魏迅, 等. 斑马鱼糖尿病模型的构建及应用进展[J]. 实验动物与比较医学, 2020, 40(6):547-552. DOI:10.3969/j.issn.1674-5817.2020.06.016 .
17	KIM J W, PARK S Y, YOU Y H, et al. Suppression of ROS production by exendin-4 in PSC attenuates the high glucose-induced islet fibrosis[J]. PLoS One, 2016, 11(12):e0163187. DOI:10.1371/journal.pone.0163187 .
18	KIM J J, LEE E, RYU G R, et al. Hypoxia increases β-cell death by activating pancreatic stellate cells within the islet[J]. Diabetes Metab J, 2020, 44(6):919-927. DOI:10.4093/dmj.2019.0181 .
19	XU X F, LIU F, XIN J Q, et al. Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)[J]. Biochem Biophys Res Commun, 2018, 501(2):365-373. DOI:10.1016/j.bbrc.2018.04.176 .
20	JIN G H, HONG W L, GUO Y Y, et al. Molecular mechanism of pancreatic stellate cells activation in chronic pancreatitis and pancreatic cancer[J]. J Cancer, 2020, 11(6):1505-1515. DOI:10.7150/jca.38616 .
21	宗毅, 廖泉, 赵玉沛. 胰腺癌实验动物模型的建立与应用[J]. 中华实验外科杂志, 2014, 31(1):210-211. DOI:10.3760/cma.j.issn.1001-9030.2014.01.078 .
22	LEE J W, KOMAR C A, BENGSCH F, et al. Genetically engineered mouse models of pancreatic cancer: The KPC model (LSL-Kras^G12D/+;LSL-Trp53^R172H/+;Pdx-1-Cre), its variants, and their application in immuno-oncology drug discovery[J]. Curr Protoc Pharmacol, 2016, 73:14.39.1-14.39.20. DOI:1002/cpph.2 .
23	POTHULA S P, XU Z H, GOLDSTEIN D, et al. Key role of pancreatic stellate cells in pancreatic cancer[J]. Cancer Lett, 2016, 381(1):194-200. DOI:10.1016/j.canlet.2015.10.035 .
24	GARG B, GIRI B, MODI S, et al. NFκB in pancreatic stellate cells reduces infiltration of tumors by cytotoxic T cells and killing of cancer cells, via up-regulation of CXCL12[J]. Gastroenterology, 2018, 155(3):880-891.e8. DOI:10.1053/j.gastro.2018.05.051 .
25	LI C X, CUI L H, YANG L, et al. Pancreatic stellate cells promote tumor progression by promoting an immunosuppressive microenvironment in murine models of pancreatic cancer[J]. Pancreas, 2020, 49(1):120-127. DOI:10.1097/MPA. 0000000000001464 .
26	VOGELMANN R, RUF D, WAGNER M, et al. Effects of fibrogenic mediators on the development of pancreatic fibrosis in a TGF-beta1 transgenic mouse model[J]. Am J Physiol Gastrointest Liver Physiol, 2001, 280(1):G164-G172. DOI: 10.1152/ajpgi.2001.280.1.G164 .
27	LI F F, CHEN B J, LI W, et al. Islet stellate cells isolated from fibrotic islet of goto-kakizaki rats affect biological behavior of beta-cell[J]. J Diabetes Res, 2016, 2016:6924593. DOI:10.1155/2016/6924593 .
28	OHNISHI H, MIYATA T, YASUDA H, et al. Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions[J]. J Biol Chem, 2004, 279(10):8873-8878. DOI: 10.1074/jbc.M309698200 .
29	WYNN T A, RAMALINGAM T R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease[J]. Nat Med, 2012, 18(7):1028-1040. DOI:10.1038/nm.2807 .
30	YANG S S, LIAN G J. ROS and diseases: role in metabolism and energy supply[J]. Mol Cell Biochem, 2020, 467(1-2):1-12. DOI:10.1007/s11010-019-03667-9 .
31	RENDRA E, RIABOV V, MOSSEL D M, et al. Reactive oxygen species (ROS) in macrophage activation and function in diabetes[J]. Immunobiology, 2019, 224(2):242-253. DOI:10.1016/j.imbio.2018.11.010 .
32	GERBER P A, RUTTER G A. The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus[J]. Antioxid Redox Signal, 2017, 26(10):501-518. DOI:10.1089/ars.2016.6755 .
33	QIN W J, LI C, ZHENG W, et al. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells[J]. Oncotarget, 2015, 6(37):39839-39854. DOI:10.18632/oncotarget.5674 .
34	AHMAD W, IJAZ B, SHABBIRI K, et al. Oxidative toxicity in diabetes and Alzheimer's disease: mechanisms behind ROS/RNS generation[J]. J Biomed Sci, 2017, 24(1):76. DOI:10.1186/s12929-017-0379-z .
35	JAKUBOWSKA M A, FERDEK P E, GERASIMENKO O V, et al. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation[J]. Open Biol, 2016, 6(8):160149. DOI:10.1098/rsob.160149 .
36	SUZUKI K. Chronic inflammation as an immunological abnormality and effectiveness of exercise[J]. Biomolecules, 2019, 9(6):223. DOI:10.3390/biom9060223 .
37	SHIMIZU K. Pancreatic stellate cells: molecular mechanism of pancreatic fibrosis[J]. J Gastroenterol Hepatol, 2008, 23():S119-S121. DOI:10.1111/j.1440-1746.2007.05296.x .
38	RAMAKRISHNAN P, LOH W M, GOPINATH S C B, et al. Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer[J]. Acta Pharm Sin B, 2020, 10(3):399-413. DOI:10.1016/j.apsb.2019.11.008 .
39	MASAMUNE A, SUZUKI N, KIKUTA K, et al. Curcumin blocks activation of pancreatic stellate cells[J]. J Cell Biochem, 2006, 97(5):1080-1093. DOI:10.1002/jcb.20698 .
40	CECI C, TENTORI L, ATZORI M G, et al. Ellagic acid inhibits bladder cancer invasiveness and in vivo tumor growth[J]. Nutrients, 2016, 8(11):744. DOI:10.3390/nu8110744 .
41	ASAUMI H, WATANABE S, TAGUCHI M, et al. Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells[J]. Eur J Clin Invest, 2006, 36(2):113-122. DOI:10.1111/j.1365-2362. 2006.01599.x .
42	SHEN K Z, FENG X W, SU R, et al. Epigallocatechin 3-gallate ameliorates bile duct ligation induced liver injury in mice by modulation of mitochondrial oxidative stress and inflammation[J]. PLoS One, 2015, 10(5):e0126278. DOI:10.1371/journal.pone.0126278 .
43	BHATT J K, THOMAS S, NANJAN M J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus[J]. Nutr Res, 2012, 32(7):537-541. DOI: 10. 1016/j.nutres.2012.06.003 .
44	INCIO J, SUBOJ P, CHIN S M, et al. Metformin reduces desmoplasia in pancreatic cancer by reprogramming stellate cells and tumor-associated macrophages[J]. PLoS One, 2015, 10(12):e0141392. DOI: 10.1371/journal.pone.0141392 .
45	GUNDEWAR C, ANSARI D, TANG L G, et al. Antiproliferative effects of curcumin analog L49H37 in pancreatic stellate cells: a comparative study[J]. Ann Gastroenterol, 2015, 28(3):391-398.

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