JAK-STAT信号通路及STAT蛋白在慢性肝病中的研究进展

王艳; 高斌

JAK-STAT信号通路及STAT蛋白在慢性肝病中的研究进展

王艳,
高斌

1. 北京大学第一医院感染疾病科
2. Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,USA

详细信息

中图分类号: R575
计量
- 文章访问数: 3327
- HTML全文浏览量: 6
- PDF下载量: 729
- 被引次数: 0
出版历程
- 出版日期: 2012-11-20

Functions of signal transducers and activators of transcription (STAT) in the liver

Wang Yan,
Gao Bin

摘要

摘要:
<正>1 JAK-STAT通路及其激活和调控1.1 JAK-STAT通路组成JAKs是一类胞浆内可溶性非受体酪氨酸蛋白激酶,分子量在120～140 kD左右。JAKs具有7个保守的同源结构域（JAK homology domain,JH）JH1～JH7。家族中已发现四个成员,即JAK1、JAK2、JAK3和Tyk2。JAKs的底物为STATs,即信号转导子和转录激活子(signal transduc-
- STAT转录因子类 /
- 干扰素类 /
- 肝炎,丙型,慢性 /
- 肝肿瘤
- STAT transcription factors /
- interferons /
- hepatitis C /
- chronic

HTML全文

参考文献(60)

[1]Gao B, Wang H, Lafdil F, et al.STAT proteins-key regulators ofanti-viral responses, inflammation, and tumorigenesis in the liver[J].J Hepatol, 2012, 57 (2) :430-441.

[2]Schindler C.Cytokines and JAK–STAT signaling[J].Exp CellRes, 1999, 253 (1) :7-14.

[3]Hong F, Jaruga B, Kim WH, et al.Opposing roles of STAT1 andSTAT3 in T cellmediated hepatitis:regulation by SOCS[J].J ClinInvest, 2002, 110 (10) :1503-1513.

[4]Ahlenstiel G, Edlich B, Hogdal LJ, et al.Early changes in natural kil-ler cell function indicate virologic response to interferon therapy for hep-atitis C[J].Gastroenterology, 2011, 141 (4) :1231-1239, e1232.

[5]Edlich B, Ahlenstiel G, Zabaleta Azpiroz A, et al.Early changesin interferon signaling define natural killer cell response and refrac-toriness to interferon-based therapy of hepatitis C[J].Hepatology, 2011, 55 (1) :39-48.

[6]Robek MD, Boyd BS, Chisari FV.Lambda interferon inhibits hepa-titis B and C virus replication[J].J Virol, 2005, 79 (6) :3851-3854.

[7]Muir AJ, Shiffman ML, Zaman A, et al.Phase 1b study of pegylat-ed interferon lambda 1 with or without ribavirin in patients withchronic genotype 1 hepatitis C virus infection[J].Hepatology, 2010, 52 (3) :822-832.

[8]Ramos EL.Preclinical and clinical development of pegylated inter-feron-lambda 1 in chronic hepatitis C[J].J Interferon CytokineRes, 2010, 30 (8) :591-595.

[9]Afdhal NH, McHutchison JG, Zeuzem S, et al.Hepatitis C pharmacoge-netics:state of the art in 2010[J].Hepatology, 2011, 53 (1) :336-345.

[10]Lange CM, Zeuzem S.IL28B single nucleotide polymorphisms in thetreatment of hepatitis C[J].J Hepatol, 2011, 55 (3) :692-701.

[11]Langhans B, Kupfer B, Braunschweiger I, et al.Interferon-lamb-da serum levels in hepatitis C[J].J Hepatol, 2011, 54 (5) :859-865.

[12]Abe H, Hayes CN, Ochi H, et al.IL28 variation affects expressionof interferon stimulated genes and peg-interferon and ribavirin ther-apy[J].J Hepatol, 2011, 54 (6) :1094-1101.

[13]Urban TJ, Thompson AJ, Bradrick SS, et al.IL28B genotype is as-sociated with differential expression of intrahepatic interferon-stim-ulated genes in patients with chronic hepatitis C[J].Hepatology, 2010, 52 (6) :1888-1896.

[14]Radaeva S, Jaruga B, Hong F, et al.Interferon-alpha activatesmultiple STAT signals and down-regulates c-Met in primary hu-man hepatocytes[J].Gastroenterology, 2002, 122 (4) :1020-1034.

[15]Torisu T, Nakaya M, Watanabe S, et al.Suppressor of cytokine sig-naling 1 protects mice against concanavalin A induced hepatitis byinhibiting apoptosis[J].Hepatology, 2008, 47 (5) :1644-1654.

[16]Lafdil F, Wang H, Park O, et al.Myeloid STAT3 inhibits T cell-mediated hepatitis by regulating T helper 1 cytokine and interleukin-17 production[J].Gastroenterology, 2009, 137 (6) :2125-2135.

[17]Klein C, Wustefeld T, Assmus U, et al.The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury[J].J Clin Invest, 2005, 115 (4) :860-869.

[18]Ogata H, Kobayashi T, Chinen T, et al.Deletion of the SOCS3 gene inliver parenchymal cells promotes epatitisinduced hepatocarcinogenesis[J].Gastroenterology, 2006, 131 (1) :179-193.

[19]Kim WH, Hong F, Radaeva S, et al.STAT1 plays an essential rolein LPS/D-galactosamineinduced liver apoptosis and injury[J].Am J Physiol Gastrointest Liver Physiol, 2003, 285 (4) :G761-768.

[20]Sun R, Park O, Horiguchi N, et al.STAT1 contributes to dsRNA inhi-bition of liver regeneration after partial hepatectomy in mice[J].Hepa-tology, 2006, 44 (4) :955-966.

[21]Jaruga B, Hong F, Kim WH, et al.IFN-{gamma}/STAT1 actsas a proinflammatory signal in T cell-mediated hepatitis via induc-tion of multiple chemokines and adhesion molecules:a critical roleof IRF-1[J].Am J Physiol Gastrointest Liver Physiol, 2004, 287 (5) :G1044-G1052.

[22]Li W, Liang X, Kellendonk C, et al.STAT3 contributes to the mi-togenic response of hepatocytes during liver regeneration[J].J BiolChem, 2002, 277 (32) :28411-28417.

[23]Dierssen U, Beraza N, Lutz HH, et al.Molecular dissection ofgp130-dependent pathways in hepatocytes during liver regenera-tion[J].J Biol Chem, 2008, 283 (15) :9886-9895.

[24]Riehle KJ, Campbell JS, McMahan RS, et al.Regulation of liverregeneration and hepatocarcinogenesis by suppressor of cytokine sig-naling 3[J].J Exp Med, 2008, 205 (1) :91-103.

[25]Radaeva S, Jaruga B, Kim WH, et al.Interferon-gamma inhibitsinterferon-alpha signalling in hepatic cells:evidence for the in-volvement of STAT1 induction and hyperexpression of STAT1 inchronic hepatitis C[J].Biochem J, 2004, 379 (Pt1) :199-208.

[26]Sakamori R, Takehara T, Ohnishi C, et al.STAT3 signaling withinhepatocytes attenuates systemic inflammatory response and lethalityin septic mice[J].Hepatology, 2007, 46 (5) :1564-1573.

[27]Wang H, Lafdil F, Wang L, et al.Hepatoprotective versus onco-genic functions of STAT3 in liver tumorigenesis[J].Am J Pathol, 2011, 179 (2) :714-724.

[28]Murray PJ.Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response[J].CurrOpin Pharmacol, 2006, 6 (4) :379-386.

[29]Kaplan MH.STAT4:a critical regulator of inflammation in vivo[J].Immunol Res, 2005, 31 (3) :231-242.

[30]Shen XD, Ke B, Zhai Y, et al.Stat4 and Stat6 signaling in hepaticischemia/reperfusion injury in mice:HO-1 dependence of Stat4disruption-mediated cytoprotection[J].Hepatology, 2003, 37 (2) :296-303.

[31]Rodriguez-Galan MC, Reynolds D, Correa SG, et al.Coexpres-sion of IL-18 strongly attenuates IL-12-induced systemic toxici-ty through a rapid induction of IL-10 without affecting its antitumorcapacity[J].J Immunol, 2009, 183 (1) :740-748.

[32]Douglas DB, Beiting DP, Loftus JP, et al.Combinatorial effects of inter-leukin 10 and interleukin 4 determine the progression of hepatic inflamma-tion following murine enteric parasitic infection[J].Hepatology, 2010, 51 (6) :2162-2171.

[33]Ryan PM, Bourdi M.Endogenous IL-4 regulates glutathione synthesisfollowing acetaminophen-induced liver injury in mice[J].Chem ResToxicol, 2012, 25 (1) :83-93.

[34]Ke B, Shen XD, Gao F, et al.Interleukin 13 gene transfer in liverischemia and reperfusion injury:role of Stat6 and TLR4 pathways incytoprotection[J].Hum Gene Ther, 2004, 15 (7) :691-698.

[35]Cao Z, Yuan Y, Jeyabalan G, et al.Preactivation of NKT cells withalpha-GalCer protects against hepatic ischemia-reperfusion injuryin mouse by a mechanism involving IL-13 and adenosine A2A re-ceptor[J].Am J Physiol Gastrointest Liver Physiol, 2009, 297 (2) :G249-G258.

[36]AdámkováL, SouckováK, Kovarík J.Transcription protein STAT1:biology and relation to cancer[J].Folia Biol (Praha) , 2007, 53 (1) :1-6.

[37]Kaplan DH, Shankaran V, Dighe AS, et al.Demonstration of aninterferon gammadependent tumor surveillance system in immuno-competent mice[J].Proc Natl Acad Sci U S A, 1998, 95 (1) :7556-7561.

[38]Lee CK, Smith E, Gimeno R, et al.STAT1 affects lymphocyte sur-vival and proliferation partially independent of its role downstream ofIFN-gamma[J].J Immunol, 2000, 164 (3) :1286-1292.

[39]Zhu ZZ, Di JZ, Gu WY, et al.Association of genetic polymor-phisms in STAT1 gene with increased risk of hepatocellular carcino-ma[J].Oncology, 2010, 78 (5-6) :382-388.

[40]Nagano H.Treatment of advanced hepatocellular carcinoma:in-traarterial infusion chemotherapy combined with interferon[J].On-cology, 2010, 78 (Suppl 1) :142-147.

[41]Haura EB, Turkson J, Jove R.Mechanisms of disease:Insights in-to the emerging role of signal transducers and activators of transcrip-tion in cancer[J].Nat Clin Pract Oncol, 2005, 2 (6) :315-324.

[42]Yu H, Jove R.The STATs of cancer--new molecular targets come ofage[J].Nat Rev Cancer, 2004, 4 (2) :97-105.

[43]He G, Karin M.NF-kappaB and STAT3-key players in liver inflam-mation and cancer[J].Cell Res, 2011, 21 (1) :159-168.

[44]Lin L, Amin R, Gallicano GI, et al.The STAT3 inhibitor NSC 74859 iseffective in hepatocellular cancers with disrupted TGF-beta signaling[J].Oncogene, 2009, 28 (7) :961-972.

[45]Zhang JF, He M, Fu WM, et al.Primatespecific miRNA-637 inhibitstumorigenesis in hepatocellular carcinoma by disrupting stat3 signaling[J].Hepatology, 2011, 54 (6) :2137-2148.

[46]Avella DM, Li G, Schell TD, et al.Regression of established hepa-tocellular carcinoma is induced by chemo-immunotherapy in an or-thotopic murine model[J].Hepatology, 2012, 55 (1) :141-152.

[47]Bard-Chapeau EA, Li S, Ding J, et al.Ptpn11/Shp2 acts as atumor suppressor in hepatocellular carcinogenesis[J].Cancer Cell, 2011, 19 (5) :629-639.

[48]Wang C, Yang W, Yan HX, et al.HBx induces tumorigenicity ofhepatic progenitor cells in DDC-treated HBx transgenic mice[J].Hepatology, 2011, 55 (1) :108-120.

[49]Naugler WE, Sakurai T, Kim S, et al.Gender disparity in liver cancerdue to sex differences in MyD88-dependent IL-6 production[J].Science, 2007, 317 (5834) :121-124.

[50]Feng GS.Conflicting roles of molecules in hepatocarcinogenesis:paradigm or paradox[J].Cancer Cell, 2012, 21 (2) :150-154.

[51]Calvisi DF.Dr.Jekyll and Mr.Hyde:a paradoxical oncogenic andtumor suppressive role of signal transducer and activator of transcrip-tion 3 in liver cancer[J].Hepatology, 2011, 54 (1) :9-12.

[52]Schneller D, Machat G, Sousek A, et al.p19 (ARF) /p14 (ARF) con-trols oncogenic functions of signal transducer and activator of transcription3 in hepatocellular carcinoma[J].Hepatology, 2011, 54 (1) :164-172.

[53]Ferbeyre G, Moriggl R.The role of Stat5 transcription factors astumor suppressors or oncogenes[J].Biochim Biophys Acta, 2011, 1815 (1) :104-114.

[54]Hosui A, Kimura A, Yamaji D, et al.Loss of STAT5causes liver fibrosis and cancer development through increased TGF-{beta}and STAT3activation[J].J Exp Med, 2009, 206 (4) :819-831.

[55]Mueller KM, Kornfeld JW, Friedbichler K, et al.Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice[J].Hepatology, 2011, 54 (4) :1398-1409.

[56]Yu JH, Zhu BM, Wickre M, et al.The transcription factors STAT5A and STAT5B negatively regulate cell proliferation through the activation of cyclin-dependent kinase inhibitor2b (Cdkn2b) and Cdkn1a expression[J].Hepatology, 2010, 52 (5) :1808-1818.

[57]Feld JJ, Modi AA, El-Diwany R, et al.S-adenosyl methionine improves early viral responses and interferon-stimulated gene in-duction in hepatitis C nonresponders[J].Gastroenterology, 2011, 140 (3) :830-839.

[58]Page BD, Ball DP, Gunning PT.Signal transducer and activator of transcription3inhibitors:a patent review[J].Expert Opin Ther Pat, 2011, 21 (1) :65-83.

[59]Tai WT, Cheng AL, Shiau CW, et al.Signal transducer and activa-tor of transcription3is a major kinase-independent target of sor-afenib in hepatocellular carcinoma[J].J Hepatol, 2011, 55 (5) :1041-1048.

[60]Rosmorduc O, Desbois-Mouthon C.Targeting STAT3in hepatocellu-lar carcinoma:Sorafenib again[J].J Hepatol, 2011, 55 (5) :957-959.

施引文献

资源附件(0)

访问统计