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浙江大学学报（医学版）
浙江大学学报（医学版）  2015, Vol. 44 Issue (2): 162-166    DOI: 10.3785/j.issn.1008-9292.2015.03.007
原著     
放射线照射的肺成纤维细胞对人脐带间充质干细胞中经典Wnt/β-catenin通路的影响
张春阳1,2, 祝艳2, 冯华松2, 陈旭昕2
1. 解放军医学院研究生队, 北京 100853;
2. 海军总医院呼吸内科, 北京 100048
Effect of irradiated human lung fibroblasts on activation of canonical Wnt/β-catenin signaling pathway in mesenchymal stem cells
ZHANG Chun-yang1,2, ZHU Yan2, FENG Hua-song2, CHEN Xu-xin2
1. Graduate Student Team of Medical School of Chinese PLA, Beijing 100853, China;
2. Department of Respiratory Medicine, Navy General Hospital, Beijing 100048, China
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摘要：

目的:体外研究放射线照射后的人肺成纤维细胞(HLFs)对人脐带间充质干细胞(HUMSCs)中经典Wnt/β-catenin信号通路的影响。方法:实验细胞分为共培养组和单纯HUMSCs组,共培养组为5Gy X射线照射后的HLFs通过Transwell系统与HUMSCs共培养。细胞培养3d后,蛋白质印迹法检测HUMSCs中GSK-3β、p-GSK-3β、FRAT1和胞核内β-catenin蛋白表达,酶联免疫吸附试验检测细胞培养上清液中WISP-1蛋白表达。 结果:共培养组HUMSCs中p-GSK-3β/GSK-3β相对比值(0.15±0.05)和FRAT1表达水平(0.48±0.07)较单纯HUMSCs组(0.55±0.05和1.16±0.13)明显下降,共培养组HUMSCs胞核内β-catenin(0.50±0.07)也较单纯HUMSCs组(2.39±0.15)明显下降;共培养组HUMSCs培养上清液中WISP-1蛋白表达[(602.23±161.47)ng/mL]较单纯HUMSCs组[(977.77±110.56)ng/mL]明显下降,差异均有统计学意义(均P<0.05)。结论:放射线照射后的HLFs对HUMSCs中经典Wnt/β-catenin通路具有抑制作用。
关键词： 成纤维细胞;  间质干细胞/生理学;  脐带;  辐射性肺炎;  Wnt蛋白质类/生物合成;  β连环素/生物合成;  胞间信号肽类和蛋白质类;  信号传导    
Abstract:

Objective: To investigate the effect of irradiated human lung fibroblasts (HLFs) on the canonical Wnt/β-catenin signaling pathway in human umbilical cord mesenchymal stem cells (HUMSCs). Methods: HUMSCs were cultured alone (single group) or co-cultured with HLFs exposed to 5Gy X-rays (co-culture group). The protein levels of GSK-3β, p-GSK-3β, FRAT1 and β-catenin in HUMSCs were examined by Western blotting 3 days after culture or co-culture. WISP-1 protein levels in conditioned medium were examined by ELISA. Results: The levels of p-GSK3β/GSK3β(0.15±0.05), FRAT1(0.48±0.07) and β-catenin(0.50±0.07)in co-cultured HUMSCs significantly decreased compared to those in single group (0.55±0.05, 1.16±0.13 and 2.39±0.15, all P<0.05).The supernatant level of WISP-1 in co-culture group was significantly decreased[(602.23±161.47)ng/mL], compared to the single group[(977.77±110.56)ng/mL, P<0.05].Conclusion: Irradiated HLFs attenuate the activation of canonical Wnt/β-catenin signaling pathway in HUMSCs in vitro.
Key words: Fibroblasts    Mesenchymal stem cells/physiology    Umbilical cord    Radiation pneumonitis    Wnt proteins/biosynthesis    Beta-catenin/biosynthesis    Intercellular signaling peptides and proteins    Signal transduction
收稿日期: 2014-11-17 出版日期: 2015-03-25
:  R146  
基金资助:

国家自然科学基金青年科学基金(81300050)
通讯作者: 冯华松(1960-),男,博士,主任医师,博士生导师,从事肺癌和肺结节病研究;E-mail:fenghs99@163.com     E-mail: fenghs99@163.com
作者简介: 张春阳(1979-),男,博士研究生,主治医师,从事肺间质病研究;E-mail:springsun27cn@163.com
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引用本文:

张春阳, 祝艳, 冯华松, 陈旭昕. 放射线照射的肺成纤维细胞对人脐带间充质干细胞中经典Wnt/β-catenin通路的影响[J]. 浙江大学学报（医学版）, 2015, 44(2): 162-166.

ZHANG Chun-yang, ZHU Yan, FENG Hua-song, CHEN Xu-xin. Effect of irradiated human lung fibroblasts on activation of canonical Wnt/β-catenin signaling pathway in mesenchymal stem cells. Journal of ZheJiang University(Medical Science), 2015, 44(2): 162-166.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2015.03.007    或    http://www.zjujournals.com/med/CN/Y2015/V44/I2/162

[1] XUE J, LI X, LU Y, et al. Gene-modified mesenchymal stem cells protect against radiation-induced lung injury [J]. Mol Ther, 2013, 21(2):456-465.
[2] ROJAS M, XU J, WOODS C R, et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung [J]. Am J Respir Cell Mol Biol, 2005,33(2):145-152.
[3] 崔瑷,代华平,戴建武,等.骨髓间充质干细胞对博来霉素致大鼠肺纤维化形成的影响[J].中华结核和呼吸杂志, 2007, 30(9):677-682. CUI Ai, DAI Hua-ping, DAI Jian-wu, et al. Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary fibrosis in rats [J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2007, 30(9):677-682. (in Chinese)
[4] YAN X, LIU Y, HAN Q, et al. Injured microenvironment directly guides the differentiation of engrafted Flk-1t mesenchymal stem cell in lung [J]. Exp Hematol, 2007, 35 (9):1466-1475.
[5] LIU A R, LIU L, CHEN S, et al. Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro [J].J Cell Physiol, 2013,228(6):1270-1283.
[6] GURUNG A, UDDIN F, HILL R P, et al. Beta-catenin is a mediator of the response of fibroblasts to irradiation [J]. Am J Pathol, 2009,174(1):248-255.
[7] 徐思慧,宋春敬,孟海建,等. 骨髓间充质干细胞分化为心肌细胞过程中Wnt信号通路的作用研究[J]. 生命科学研究, 2014,18(6):539-542. XU Si-hui, SONG Chun-jing, MENG Hai-jian, et al. The role of Wnt signaling pathway in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) to cardiomyocytes [J]. Life Science Research, 2014,18(6):539-542.(in Chinese)
[8] FORDE J E, DALE T C. Glycogen synthase kinase 3:a key regulator of cellular fate [J]. Cell Mol Life Sci, 2007, 64(15):1930-1944.
[9] GAO L R, ZHANG N K, DING Q A, et al. Common expression of stemness molecular markers and early cardiac transcription factors in human Wharton's jelly-derived mesenchymal stem cells and embryonic stem cells [J]. Cell Transplant, 2013, 22(10):1883-1900.
[10] LI Y Y,LIN D J,GAO G X.Pathogenesis of radiation-induced lung injury [J]. Int J Respir, 2012,21(10):784-788.
[11] OKOYE U C, MALBON C C, WANG H Y. Wnt and Frizzled RNA expression in human mesenchymal and embryonic (H7) stem cells [J]. J Mol Signal, 2008, 3:16. doi:10.1186/1750-2187-3-16.
[12] KASAI M, SATOH K, AKIYAMA T. Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs [J]. Genes Cells, 2005, 10(8):777-783.
[13] VAN AMERONGEN R, BERNS A. Re-evaluating the role of Frat in Wnt-signal transduction [J]. Cell Cycle, 2005, 4(8):1065-1072.
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