IL-13Rα2作为功能受体介导信号转导的研究进展

doi:10.3969/j.issn.1000-4718.2014.08.031

摘要
图/表
参考文献(0)
相关文章 (15)

全文: PDF (732 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	金旗
	熊丽霞

关键词 ： IL-13受体α2, 信号转导, 分子靶向治疗

Abstract：

IL-13 is a pleiotropic cytokine mainly secreted by activated Th2 cells. It has 2 receptors, IL-13Rα1 and IL-13Rα2. The latter had been thought to serve exclusively as a decoy receptor for a long period of time due to its short cytoplasmic tail and lack of signal transduction structure. Since Fichtner-Feigl reported in Nature Medicine that IL-13 is involved in induction of TGF-β production and tissue fibrosis through IL-13Rα2-mediated signaling pathway, it was found that IL-13Rα2 has more sophisticated functions than just a simple decoy receptor as more and more researches have explored its signaling functions. This review combines the most advanced research results with previous investigation and discusses the gene structure, expression, production, distribution, subtype conversion and possible signal pathways mediated by this receptor. More importantly, the connection with human diseases and the applications in disease diagnosis and molecule targeted therapy for cancer are also discussed.

Key words： IL-13 receptor alpha 2 Signal transduction Molecular targeted therapy

收稿日期: 2013-11-20 出版日期: 2014-08-15

中图分类号:

R363

基金资助:

国家自然科学基金资助项目（No. 81200069）；江西省大学生创新创业训练计划项目（No. 201310403033）；江西省教育厅资助项目（No.GJJ12056）；江西省卫生厅资助项目（No.20132020）

通讯作者: 熊丽霞 E-mail: xionglixia8888@aliyun.com

引用本文:

金旗,熊丽霞. IL-13Rα2作为功能受体介导信号转导的研究进展[J]. 中国病理生理杂志, 2014, 30(8): 1513-1518. JIN Qi, XIONG Li-xia. IL-13Rα2 as a functional receptor mediates signal transduction. Chin J Pathophysiol, 2014, 30(8): 1513-1518.

链接本文:

http://www.cjpp.net/CN/10.3969/j.issn.1000-4718.2014.08.031 或 http://www.cjpp.net/CN/Y2014/V30/I8/1513

［1］	Joshi BH, Hogaboam C, Dover P, et al. Role of interleukin-13 in cancer, pulmonary fibrosis, and other TH2-type diseases［J］. Vitam Horm, 2006, 74:479-504.
［2］	Strober W, Kitani A, Fichtner-Feigl S, et al. The signaling function of the IL-13Rα2 receptor in the development of gastrointestinal fibrosis and cancer surveillance［J］. Curr Mol Med, 2009, 9(6):740-750.
［3］	Fichtner-Feigl S, Strober W, Kawakami K, et al. IL-13 signaling through the IL-13α2 receptor is involved in induction of TGF-beta1 production and Fibrosis［J］. Nat Med, 2006, 12(1):99-106.
［4］	Wu AH,Low WC. Molecular cloning and identification of the human interleukin 13 α 2 receptor (IL-13Rα2) promoter［J］. Neuro Oncol, 2003, 5(3):179-187.
［5］	Caput D, Laurent P, Kaghad M, et al. Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor alpha chain［J］. J Biol Chem, 1996, 271(28):16921-16926.
［6］	Wang W, Shen YX, Li J, et al. Enhanced expression of the decoy receptor IL-13Rα2 in macrophages of Schistosoma japonicum-infected mice［J］. Chin Med J, 2009, 122(14):1650-1654.
［7］	Arima K, Sato K, Tanaka G, et al. Characterization of the interaction between interleukin-13 and interleukin-13 receptors［J］. J Biol Chem, 2005, 280(26):24915-24922.
［8］	熊慧玲, 李文林, 石小玉. 白细胞介素13受体α2在纤维化疾病中的研究进展［J］. 南昌大学学报:(医学版), 2012, 52(4):98-100.
9］	Donaldson DD, Whitters MJ, Fitz LJ, et al. The murine IL-13 receptor alpha 2:molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1［J］. J Immunol, 1998, 161(5):2317-2324.
［10］	Andrews AL, Nordgren IK, Kirby I, et al. Cytoplasmic tail of IL-13Rα2 regulates IL-4 signal transduction［J］. Biochem Soc Trans, 2009, 37(Pt 4):873-876.
［11］	David M, Ford D, Bertoglio J, et al. Induction of the IL-13 receptor alpha2-chain by IL-4 and IL-13 in human keratinocytes: involvement of STAT6, ERK and p38 MAPK pathways［J］. Oncogene, 2001, 20(46): 6660-6668.
［12］	Mintz A, Gibo DM, Slagle-Webb B, et al. IL-13Rα2 is a glioma-restricted receptor for interleukin-13［J］. Neoplasia, 2002, 4(5):388-399.
［13］	Andrews AL, Nasir T, Bucchieri F, et al. IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts［J］. J Allergy Clin Immunol, 2006, 118(4):858-865.
［14］	Zheng T, Zhu Z, Liu W, et al. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro［J］. J Allergy Clin Immunol, 2003, 111(4):720-728.
［15］	Yoshikawa M, Nakajima T, Tsukidate T, et al. TNF-alpha and IL-4 regulate expression of IL-13 receptor alpha2 on human fibroblasts［J］. Biochem Biophys Res Commun, 2003, 312(4): 1248-1255.
［16］	Zhao Y, He D, Zhao J, et al. Lysophosphatidic acid induces interleukin-13 (IL-13) receptor alpha2 expression and inhibits IL-13 signaling in primary human bronchial epithelial cells［J］. J Biol Chem, 2007, 282(14): 10172-10179.
［17］	Daines MO, Tabata Y, Walker BA, et al. Level of expression of IL-13R alpha 2 impacts receptor distribution and IL-13 signaling［J］. J Immunol, 2006, 176(12):7495-7501.
［18］	Chen W, Sivaprasad U, Tabata Y, et al. IL-13R alpha 2 membrane and soluble isoforms differ in humans and mice［J］. J Immunol, 2009, 183(12):7870-7876.
［19］	Daines MO, Hershey GK. A novel mechanism by which interferon-gamma can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor alpha-2 and their rapid mobilization by interferon-gamma［J］. J Biol Chem, 2002, 277(12):10387-10393.
［20］	Daines MO, Chen W, Tabata Y, et al. Allergen-depen-dent solubilization of IL-13 receptor alpha2 reveals a novel mechanism to regulate allergy［J］. J Allergy Clin Immunol, 2007, 119(2):375-383.
［21］	Chen W, Sivaprasad U, Gibson AM, et al. IL-13 receptor α2 contributes to development of experimental allergic asthma［J］. J Allergy Clin Immunol, 2013, 132(4):951-958.
［22］	Fichtner-Feigl S, Young CA, Kitani A, et al. IL-13 signaling via IL-13Rα2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis［J］. Gastroenterology, 2008, 135(6):2003-2013.
［23］	Brunner SM, Schiechl G, Kesselring R, et al. IL-13 signaling via IL-13Rα2 triggers TGF-β1-dependent allograft fibrosis［J］. Transplant Res, 2013, 2:16.
［24］	Allahverdian S, Singhera GK, Dorscheid DR. IL-13 signaling through the IL-13 receptor α2 mediates airway epithelial wound repair［J］. Am J Respir Crit Care Med, 2009,179:A4272.
［25］	Yang JS, Allahverdian S, Singhera GK, et al. IL-13Rα2/AP-1 complex signalling mediates airway epithelial repair without effects on remodeling pathways［J］. Allergy Asthma Clin Immunol, 2010, 6(Suppl 3):P27.
［26］	Cho WK, Lee CM, Kang MJ, et al. IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension［J］. Am J Physiol Lung Cell Mol Physiol, 2013, 304(2):L112-L124.
［27］	Fujisawa T, Joshi BH, Puri RK. IL-13 regulates cancer invasion and metastasis through IL-13Rα2 via ERK/AP-1 pathway in mouse model of human ovarian cancer［J］. Int J Cancer, 2012, 131(2):344-356.
［28］	Fujisawa T, Joshi B, Nakajima A, et al. A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis［J］. Cancer Res, 2009, 69(22):8678-8685.
［29］	Shimamura T, Fujisawa T, Husain SR, et al. Interleukin 13 mediates signal transduction through interleukin 13 receptor alpha2 in pancreatic ductal adenocarcinoma: role of IL-13 Pseudomonas exotoxin in pancreatic cancer therapy［J］. Clin Cancer Res, 2010, 16(2):577-586.
［30］	Strober W, Kitani A, Fichtner-Feigl S, et al. The signaling function of the IL-13Rα2 receptor in the development of gastrointestinal fibrosis and cancer surveillance［J］. Curr Mol Med, 2009, 9(6):740-750.
［31］	Hall B, Nakashima H, Sun ZJ, et al. Targeting of interleukin-13 receptor α2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-β and PTEN signaling［J］. J Transl Med, 2013, 11:45.
［32］	Kawakami M, Kawakami K, Puri RK. Intratumor administration of interleukin 13 receptor-targeted cytotoxin induces apoptotic cell death in human malignant glioma tumor xenografts［J］. Mol Cancer Ther, 2002, 1(12): 999-1007.
［33］	Nakashima H, Terabe M, Berzofsky JA, et al. A novel combination immunotherapy for cancer by IL-13Rα2-targeted DNA vaccine and immunotoxin in murine tumor models［J］. J Immunol, 2011, 187(10):4935-4946.
［34］	Hou L, Du J, Wang J, et al. Expression of IL-13Rα2 in liver cancer cells and its effect on targeted therapy of liver cancer［J］. J Cancer Res Clin Oncol, 2010, 136(6):839-846.
［35］	Hsi LC, Kundu S, Palomo J, et al. Silencing IL-13Rα2 promotes glioblastoma cell death via endogenous signaling［J］. Mol Cancer Ther, 2011, 10(7):1149-1160.
［36］	Lee CG, Homer RJ, Zhu Z, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β１［J］. J Exp Med, 2001, 194(6):809-821.