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Role of ZFP580 in acute pancreatitis induced by caerulein through endoplasmic reticulum stress pathway |
ZI Li1,2, LIU Guanglin1,2, ZHANG Wencheng1,2, XIA Shihaii1,2, XU Wei1,2 |
1. Department of Gastroenterology, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China; 2. Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China |
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Abstract Objective To investigate the role of zinc finger protein 580 (ZFP580) in acute pancreatitis (AP) induced by caerulein through endoplasmic reticulum (ER) stress pathway, and provide a new therapeutic target for AP treatment.Methods MTT method was used to detect cell viability. RT-PCR and Western Blot were used to detect endoplasmic reticulum stress-related mRNA and the protein expression of ZFP580 in AP model. IRE1 inhibitor (MKC-3946) was used to observe the position of ZFP580 in endoplasmic reticulum stress related signaling pathway. After Silencing ZFP580, Hochest33342 staining and WB, RT-PCT method were used to investigate the effect of ZFP580 on the apoptosis-necrosis process.Results After using cerulein to stimulate acute pancreatitis in AR42J cells, the endoplasmic reticulum stress occurred. 8 hours later, the expression of ZFP580 started to increase (showing a time-dependent increase). After using IRE1 inhibitor (MKC-3946), the expression of ZFP580 was significantly lower than that of the group without MKC-3946 treatment (P<0.05). After silencing ZFP580, the expression of XBP-1s significantly decreased. At the same time, RT-PCR and Western blot results showed that the expression of Chop in the si-ZFP580 group was significantly higher than that in the normal AP group, while the expression of Caspase-3 was lower than that in the normal AP group. The result of Hochest staining revealed that the proportion of necrotic cells in the si-ZFP580 group was significantly higher than that in the normal AP group.Conclusions ZFP580 which may be located between IRE1 and XBP-1s may play a protective role in regulating the severity of AP by improving the apoptosis-necrosis ratio.
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Received: 23 June 2021
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[1] |
Peery A F, Dellon E S, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update[J]. Gastroenterology, 2012, 143(5): 1179-1187.
|
[2] |
Steinberg W, Tenner S. Acute pancreatitis[J]. N Engl J Med, 1994, 330 (17): 1198-2100.
|
[3] |
Sendler M, Dummer A, Weiss F U, et al. Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice[J]. Gut, 2013, 62(3): 430-9.
|
[4] |
Barrera K, Stanek A, Okochi K, et al. Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis[J]. World J Gas Path, 2018, 9(2):37-46.
|
[5] |
Zhang J, Wang Y, Liu B, et al. Ligustrum vulgare activity of lextracts against acute pancreatitis in murine models by regulation of P38 MAPK and NF-κB signaling pathways[J]. Saudi J Biol Sci, 2022, 29 (1): 273-278.
|
[6] |
Singh V P, Chari S T. Protease inhibitors in acute pancreatitis: lessons from the bench and failed clinical trial[J]. Gastroenterology, 2005, 128 (7): 2172-2174.
|
[7] |
Zhan X, Wan J, Zhang G, et al. Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice[J]. Am J Physiol Gas, 2019, 316 (6): G816-G825.
|
[8] |
Fu X, Zhong X, Chen X, et al. GSK-3β activates to aggravate caerulein-induced early acute pancreatitis in mice [J]. Ann Transl Med, 2021, 9 (22): 1695.
|
[9] |
Grey M J. Proteomic study defines how alcohol alters ER structure and redox proteome to trigger ER stress and acinar cell pathology in pancreatitis[J]. Cell Mol Gas Hepatol, 2018, 5 (4): 640-641.
|
[10] |
Xia S, Wang J, Kalionis B, et al. Genistein protects against acute pancreatitis via activation of an apoptotic pathway mediated through endoplasmic reticulum stress in rats[J]. Biochem Biophys Res Commun, 2018, 509(2): 421-428.
|
[11] |
Gukovskaya A S, Gorelick F S, Groblewski G E, et al. Recent insights into the pathogenic mechanism of pancreatitis: role of acinar cell organelle disorders[J]. Pancreas, 2019, 48 (4): 459-470.
|
[12] |
Feng S, Wei Q, Hu Q, et al. Research progress on the relationship between acute pancreatitis and calcium overload in acinar cells[J]. Dig Dis Sci, 2019, 64 (1): 25-38.
|
[13] |
张文成,陈保生,吴 刚,等. 低密度脂蛋白诱导下调的新基因cDNA的克隆及组织表达[J]. 基础医学与临床,2003, 23 (3): 279-282.
|
[14] |
孟祥艳, 孙慧燕,孔麟麟,等. 锌指基因ZFP580在大鼠心肌缺血损伤中的表达[J]. 武警后勤学院学报,2010, 19(1):1-3.
|
[15] |
Ding S P, Li J C, Jin C. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide[J]. World J Gas, 2003, 9 (3): 584-589.
|
[16] |
Lee A H, Chu G C, Iwakoshi N N, et al. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands [J]. EMBO J, 2005, 24(24): 4368-4380.
|
[17] |
Hess D A, Humphrey S E, Ishibashi J, et al. Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice[J]. Gastroenterology, 2011, 141(4): 1463-1472.
|
[18] |
Rasheva V, Domingos P. Cellular responses to endoplasmic reticulum stress and apoptosis[J]. Apoptosis, 2009, 14(8): 996-1007.
|
[19] |
Liu Y, Yang L, Chen K, et al. Knockdown of GRP78 promotes apoptosis in pancreatic acinar cells and attenuates the severity of cerulein and LPS induced pancreatic inflammation[J]. PLoS One, 2014, 9(3): 23-29.
|
[20] |
He S, Wang L, Miao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha[J]. Cell, 2009, 137(6): 1100-1111.
|
[21] |
Wang J, Chen G, Gong H, et al. Amelioration of experimental acute pancreatitis with Dachengqi decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell[J]. PLoS One, 2012, 7(7): 40-47.
|
[22] |
Lomberk G, Urrutia R. Primers on molecular pathways-caspase pathway[J]. Pancreatology, 2009, 9(1-2): 6-8.
|
[23] |
Jacob T G, Sreekumar V I, Roy T S, et al. Electron-microscopic evidence of mitochondriae containing macroautophagy in experimental acute pancreatitis: implications for cell death[J]. Pancreatology, 2014, 14(6): 454-458.
|
[24] |
Yu C, Merza M, Luo L, et al. Inhibition of Ras signalling reduces neutrophil infiltration and tissue damage in severe acute pancreatitis[J]. Eur J Pharmacol, 2015, 746(1): 245-251.
|
[25] |
Cai Y, Shen Y, Xu G, et al. TRAM1 protects AR42J cells from caerulein-induced acute pancreatitis through ER stress-apoptosis pathway[J]. Cell Dev Biol Anim, 2016, 52(5): 530-536.
|
[26] |
Chen H, Zhang G, Gong A, et al. Role of acinar cell apoptosis and expression of bax and caspase-8 in rats with acute pancreatitis[J]. World Chinese J Digestology, 2007, 15(1): 1067-1073.
|
[27] |
Fonseca S G, Lipson K L, Urano F, et al. Endoplasmic reticulum stress signaling in pancreatic β-cells[J]. Anti Red Sign, 2007, 9(12): 2335-2344.
|
[28] |
Oyadomari S, Mori M. Roles of Chop/GADD153 in endoplasmic reticulum stress[J]. Cell Death And Dif, 2004, 11(4): 381-389.
|
[29] |
Han J, Back S H, Hur J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death[J]. Nat Cell Biol, 2013, 15(5): 481-490.
|
[30] |
Di S F, Ferraro E, Tufi R, et al. Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but Caspase 12-independent mechanism[J]. J Biol Chem, 2006, 281(5): 2693-2700.
|
[31] |
Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β[J]. Nature, 2000, 403(6765):98-103.
|
[32] |
Chen F. JNK-induced apoptosis, compensatory growth and cancer stem cells[J]. Cancer Res, 2012, 72(2): 379-386.
|
[33] |
Williams J A, Sans M D, Tashiro M, et al. Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells[J]. Pharmacol Toxicol, 2002, 91(6): 297-303.
|
[1] |
. [J]. Med. J. Chin. Peop. Armed Poli. Forc., 2019, 30(3): 260-264. |
|
|
|
|