胰岛再生源蛋白与肝脏疾病和肝再生

王改平 陈萌 赵聪聪 陈莎莎 徐存拴

解剖学报 ›› 2017, Vol. 48 ›› Issue (4) : 488-492.

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解剖学报 ›› 2017, Vol. 48 ›› Issue (4) : 488-492. DOI: 10.16098/j.issn.0529-1356.2017.04.021
综述

胰岛再生源蛋白与肝脏疾病和肝再生

  • 王改平1,2* 陈萌1,2 赵聪聪1,2陈莎莎1,2徐存拴1,2
作者信息 +

Roles of regenerating islet-derived protein family in liver diseases and liver regeneration

  • WANG Gai-ping1,2* CHEN Meng1,2 ZHAO Cong-cong1,2 CHEN Sha-sha1,2 XU Cun-shuan1,2
Author information +
文章历史 +

摘要

胰岛再生源蛋白 (Reg) 是相对分子质量为16kD的分泌型蛋白,属于C类凝集素超家族成员。Reg蛋白是1个多功能分子,主要参与调控胰腺、胃、肠和肝脏中细胞的生长和增殖,在消化性疾病及癌症的发展和预后中发挥重要作用。我们主要综述了Reg对肝脏疾病和肝再生调控的研究进展,包含其在消化性疾病中介导的信号通路,为开展Reg在相关疾病诊疗及促进肝再生中的应用研究提供重要理论基础。

Abstract

Regenerating islet-derived protein (Reg) are a group of 16 kD secretory proteins and belong to the C-type lectin superfamily. Reg proteins are multi-functional molecules, which are mainly involved in regulating cell growth and proliferation in pancreas, stomach, intestine and liver, and play an important role in the development and prognosis of digestive diseases and cancers. We reviewed research progress of the complex roles of Reg family in liver diseases and liver regeneration, including Reg family-mediated signaling pathways in digestive diseases, and laid an important theoretical foundation for application of Reg family in the diagnosis, treatment of digestive diseases and promotion of liver regeneration.

关键词

胰岛再生源蛋白 / 肝脏疾病 / 肝再生

Key words

Regenerating islet-derived protein / Liver disease / Liver regeneration

引用本文

导出引用
王改平 陈萌 赵聪聪 陈莎莎 徐存拴. 胰岛再生源蛋白与肝脏疾病和肝再生[J]. 解剖学报. 2017, 48(4): 488-492 https://doi.org/10.16098/j.issn.0529-1356.2017.04.021
WANG Gai-ping CHEN Meng ZHAO Cong-cong CHEN Sha-sha XU Cun-shuan. Roles of regenerating islet-derived protein family in liver diseases and liver regeneration[J]. Acta Anatomica Sinica. 2017, 48(4): 488-492 https://doi.org/10.16098/j.issn.0529-1356.2017.04.021

参考文献

[1]De Caro A, Lohse J, Sarles H. Characterization of a protein isolated from pancreatic calculi of men suffering from chronic calcifying pancreatitis [J]. Biochem Biophys Res Commun, 1979, 87(4): 1176-1182.
[2]Closa D, Motoo Y, Iovanna JL. Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine [J]. World J Gastroenterol, 2007, 13(2): 170-174.
[3]Jiang ZW, Li ChW, Lei H, et al. Function and regulatory mechanism of regenerating Islet-derived protein(Reg)in tissue repair [J]. Chinese Journal of Cell Biology, 2012, 34(1):1-10. (in Chinese)
蒋子威, 李长伟, 雷虎, 等. 胰岛再生源蛋白(Reg)在组织修复中的功能和调控机制 [J]. 中国细胞生物学学报, 2012, 34(1): 1-10.
[4]Li JL, Cui W. Which gene, Reg2 or Reg3beta, was targeted that affected liver regeneration [J]? Hepatology, 2007, 45(6): 1584-1585.
[5]Haldipur P, Dupuis N, Degos V, et al. HIP/PAP prevents excitotoxic neuronal death and promotes plasticity [J]. Ann Clin Transl Neurol, 2014, 1(10): 739-754.
[6]van Ampting MT, Loonen LM, Schonewille AJ, et al. Intestinally secreted C-type lectin Reg3b attenuates salmonellosis but not listeriosis in mice [J]. Infect Immun, 2012, 80(3): 1115-1120.
[7]Loonen LM, Stolte EH, Jaklofsky MT, et al. REG3gamma-deficient mice have altered mucus distribution and increased mucosal inflammatory responses to the microbiota and enteric pathogens in the ileum [J]. Mucosal Immunol, 2014, 7(4): 939-947.
[8]Wang Y, Jacovetti C, Li B, et al. Coordinated age-dependent and pancreatic-specific expression of mouse Reg2 Reg3alpha, and Reg3beta genes [J]. Growth Factors, 2011, 29(2-3): 72-81.
[9]Matsumoto S, Konishi H, Maeda R, et al. Expression analysis of the regenerating gene (Reg) family members Reg-IIIbeta and RegIIIgamma in the mouse during development [J]. J Comp Neurol, 2012, 520(3): 479-494.
[10]Azman J, Starcevic Klasan G, Ivanac D, et al. Reg Ⅳ protein and mRNA expression in different rat organs [J]. Acta Histochem, 2011, 113(8): 793-797.
[11]van Beelen Granlund A, Ostvik AE, Brenna O, et al. REG gene expression in inflamed and healthy colon mucosa explored by in situ hybridisation [J]. Cell Tissue Res, 2013, 352(3): 639-646.
[12]Kobayashi S, Akiyama T, Nata K, et al. Identification of a receptor for reg (regenerating gene) protein, a pancreatic beta-cell regeneration factor [J]. J Biol Chem, 2000, 275(15): 10723-10726.
[13]Nata K, Liu Y, Xu L, et al. Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III [J]. Gene, 2004, 340(1): 161-170.
[14]Levetan CS, Upham LV, Deng S, et al. Discovery of a human peptide sequence signaling islet neogenesis [J]. Endocr Pract, 2008, 14(9): 1075-1083.
[15]Acquatella-Tran Van Ba I, Marchal S, Francois F, et al. Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin tumor-like 3 (EXTL3) receptor [J]. J Biol Chem, 2012, 287(7): 4726-4739.
[16]Kiji T, Dohi Y, Takasawa S, et al. Activation of regenerating gene Reg in rat and human hearts in response to acute stress [J]. Am J Physiol Heart Circ Physiol, 2005, 289(1): H277-284.
[17]Mitani Y, Oue N, Matsumura S, et al. Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy [J]. Oncogene, 2007, 26(30): 4383-4393.
[18]Bishnupuri KS, Luo Q, Murmu N, et al. Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas [J]. Gastroenterology, 2006, 130(1): 137-149.
[19]Satomura Y, Sawabu N, Mouri I, et al. Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay[J]. J Gastroenterol, 1995, 30(5): 643-650.
[20]Christa L, Simon M T, Brezault-Bonnet C, et al. Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells [J]. Am J Pathol, 1999, 155(5): 1525-1533.
[21]Lieu HT, Batteux F, Simon MT, et al. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice [J]. Hepatology, 2005, 42(3): 618-626.
[22]Zhang HB, Luo HC, Xin XJ, et al. Up-regulated Reg proteins induced by interleukin-22 treatment ameliorate acute liver injury in rat model [J]. Int J Clin Exp Med, 2015, 8(1): 1253-1258.
[23]White P, Brestelli JE, Kaestner KH, et al. Identification of transcriptional networks during liver regeneration [J]. J Biol Chem, 2005, 280(5): 3715-3722.
[24]Wang J, Koyota S, Zhou X, et al. Expression and localization of regenerating gene I in a rat liver regeneration model [J]. Biochem Biophys Res Commun, 2009, 380(3): 472-477.[25]Simon MT, Pauloin A, Normand G, et al. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway [J]. FASEB J, 2003, 17(11): 1441-1450.
[26]Lieu HT, Simon MT, Nguyen-Khoa T, et al. Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice [J]. Hepatology, 2006, 44(6): 1452-1464.
[27]Moniaux N, Song H, Darnaud M, et al. Human hepatocarcinoma-intestine-pancreas or pancreatitis-associated protein cures fas-induced acute liver failure in mice by attenuating free-radical damage in injured livers [J]. Hepatology, 2011, 53(2): 618-627.
[28]Moniaux N, Darnaud M, Garbin K, et al. The reg3alpha (HIP/PAP) lectin suppresses extracellular oxidative stress in a murine model of acute liver failure [J]. PLoS One, 2015, 10(5): e0125584.
[29]Demaugre F, Philippe Y, Sar S, et al. HIP/PAP, a C-type lectin overexpressed in hepatocellular carcinoma, binds the RII alpha regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signalling [J]. Eur J Biochem, 2004, 271(19): 3812-3820.
[30]Huang Y, Liu D, Jiang L, et al. Expression of MAPK / ERK1 and STAT3 in LPS -induced glandular cystitis model [J]. Acta Anatomica Sinica, 2012, 43(6):807-812. (in Chinese)
黄瑛, 柳达, 姜罗, 等. MAPK/ERK1与STAT3在脂多糖诱导的腺性膀胱炎动物模型中的表达 [J]. 解剖学报, 2012, 43(6): 807-812.
[31]Sekikawa A, Fukui H, Fujii S, et al. REG Ialpha protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells [J]. Carcinogenesis, 2008, 29(1): 76-83.
[32]Liu X, Wang J, Wang H, et al. REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop [J]. Cancer Lett, 2015, 362(1): 45-60.
[33]Folch-Puy E, Granell S, Dagorn JC, et al. Pancreatitis-associated protein I suppresses NF-kappa B activation through a JAK/STAT-mediated mechanism in epithelial cells [J]. J Immunol, 2006, 176(6): 3774-3779.
[34]Loncle C, Bonjoch L, Folch-Puy E, et al. IL17 Functions through the novel REG3beta-JAK2-STAT3 inflammatory pathway to promote the transition from chronic pancreatitis to pancreatic cancer [J]. Cancer Res, 2015, 75(22): 4852-4862.
[35]Yin G, Du J, Cao H, et al. Reg3g promotes pancreatic carcinogenesis in a murine model of chronic pancreatitis [J]. Dig Dis Sci, 2015, 60(12): 3656-3668.
[36]Guo WW, Bai ShL, Wang J, et al. Expression of NF-κB and regulatory activated normal T cells and expression of chemokines in ascending aortic aneurysm formation [J]. Acta Anatomica Sinica, 2010, 41(1): 75-79. (in Chinese)
郭万伟, 柏树令, 王军, et al. NF-κB及调节活化正常T细胞表达和趋化因子在升主动脉瘤形成中的表达 [J]. 解剖学报, 2010, 41(1): 75-79.
[37]Yang X, Jin H, Liu K, et al. A novel peptide derived from human pancreatitis-associated protein inhibits inflammation in vivo and in vitro and blocks NF-kappa B signaling pathway [J]. PLoS One, 2011, 6(12): e29155.
[38]Gironella M, Calvo C, Fernandez A, et al. Reg3beta deficiency impairs pancreatic tumor growth by skewing macrophage polarization [J]. Cancer Res, 2013, 73(18): 5682-5694.[39]Viterbo D, Bluth MH, Lin YY, et al. Pancreatitis-associated protein 2 modulates inflammatory responses in macrophages [J]. J Immunol, 2008, 181(3): 1948-1958.
[40]Kadowaki Y, Ishihara S, Miyaoka Y, et al. Reg protein is overexpressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth [J]. FEBS Lett, 2002, 530(1-3): 59-64.
[41]Wakita A, Motoyama S, Sato Y, et al. REG Ialpha activates c-Jun through MAPK pathways to enhance the radiosensitivity of squamous esophageal cancer cells [J]. Tumour Biol, 2015, 36(7): 5249-5254.
[42]Mueller CM, Zhang H, Zenilman ME. Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells [J]. J Surg Res, 2008, 150(1): 137-143.
[43]Ferres-Maso M, Sacilotto N, Lopez-Rodas G, et al. PAP1 signaling involves MAPK signal transduction [J]. Cell Mol Life Sci, 2009, 66(13): 2195-2204.
[44]Bishnupuri KS, Sainathan SK, Bishnupuri K, et al. Reg4-induced mitogenesis involves Akt-GSK3beta-beta-Catenin-TCF-4 signaling in human colorectal cancer [J]. Mol Carcinog, 2014, 53 (Suppl 1): E169-180.

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