Wnt诱导分泌蛋白-1介导肝纤维化发生的实验及临床观察

李玮; 熊伍军; 简易成; 江鸣; 何益; 刘雁冰

Wnt诱导分泌蛋白-1介导肝纤维化发生的实验及临床观察

同济大学附属东方医院消化内科

详细信息

中图分类号: R575.2
计量
- 文章访问数: 3391
- HTML全文浏览量: 21
- PDF下载量: 814
- 被引次数: 0
出版历程
- 出版日期: 2011-06-20

Experimental and clinical study of the role of Wnt induced secreted protein-1 in liver fibrosis

摘要

摘要: 目的探讨Wnt诱导分泌蛋白-1（WISP-1）在大鼠肝纤维化模型表达水平变化及其与慢性肝病患者病程进展的相关性。方法四氯化碳CCl4皮下注射制作大鼠肝纤维化动物模型,取正常组、造模8周组、造模12周组大鼠肝组织,利用免疫组化观察大鼠肝组织WISP-1表达水平的变化,光镜下半定量分析;收集健康体检者血清20例,慢性HBV携带者患者血清20例,乙型肝炎肝硬化患者血清60例,利用ELISA测定血清WISP-1水平变化,利用放射免疫检测血清透明质酸（HA）、层粘蛋白（LN）、前Ⅲ型胶原（PⅢP）、Ⅳ型胶原（CⅣ）水平,分析WISP-1水平与血清肝纤维化指标的相关性。结果造模8、12周组WISP-1表达水平分别为11.0±2.4、23.8±4.8,与正常组2.3±2.1比较差异具有统计学意义（P<0.05）;慢性HBV携带者、乙型肝炎肝硬化患者血清WISP-1水平分别为（65.5±18.8）、（71.2±18.2）ng/ml,与健康对照组（57.3±15.2）ng/ml比较差异具有统计学意义（P<0.05）,相关分析表明WISP-1与HA、LN、PⅢP、CⅣ相关系数分别为0.41、0...
- 肝硬化 /
- 肝炎,慢性 /
- Wnt诱导分泌蛋白-1
Abstract: Objective To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in experimental liver fibrosis in rats and to determine whether it is correlated with the progress of human chronic liver diseases.Methods Experimental liver fibrosis was induced in male Sprague-Dawley rats with CCl4.At the end of the 8 wk, 12wk animals were sacrificed, liver tissue were collected respectively for pathological examination and immunohistochemistry.Serums were collected from 20 individuals, 20 chronic hepatitis B patients and 60 liver cirrhosis patients.The serum levels of WISP-1 were examined with ELISA.HA, LN, PⅢP and CⅣ were examined with radioimmunology assay.Analysis of the correlation between serum WISP-1, and HA, LN, PⅢP, CⅣ were made.Results The expression levels of WISP-1 in the 8wk group (11.0±2.4) and 12wk group (23.8±4.8) are significantly higher than that in the normal group (2.3±2.1) (P<0.05) .The serum WISP-1 level of chronic hepatitis B patients [ (65.5±18.8) ng/ml] and liver cirrhosis [ (71.2±18.2) ng/ml] are markedly higher than that in the healthy control group[ (57.3±15.2) ng/ml] (P<0.05) .At the same time, the serum WISP-1 level is positively correlated with HA (r=0.41) , LN (r=0.53) , PⅢP (r=0.50) , CⅣ (r=0.64) respectively (P<0.05) .Conclusion Aberrant level of WISP-1 expression plays a role in liver fibrogenesis, serum WISP-1 level is correlated with the progress of human chronic liver diseases.It is needed to have further study of the effect and mechanism of WISP-1 in liver fibrogenesis.
- liver cirrhosis /
- hepatitis /
- chronic

HTML全文

参考文献(11)

[1]MacDonald BT, Tamai K, He X.Wnt/beta-catenin signaling:components, mechanisms, and diseases[J].Dev Cell, 2009, 17 (1) :9-26.

[2]简易成, 熊伍军.Wnt诱导分泌蛋白-1与器官纤维化[J].国际消化病杂志, 2010, 30 (5) :297-299.

[3]Knigshoff M, Wilhelm J, Jahn A, et al.Wnt-inducible protein (WISP-1) is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis[J].Eur Respir Rev, 2006, 15 (101) :180-181.

[4]Selman M, Pardo A, Barrera L, et al.Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis[J].Am J Respir Crit Care Med, 2006, 173 (2) :188-198.

[5]Knigshoff M, Kramer M, Balsara N, et al.WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis[J].J Clin Invest, 2009, 119 (4) :772-787.

[6]Colston JT, de la Rosa SD, Koehler M, et al.Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor[J].Am J Physiol Heart Circ Physiol, 2007, 293 (3) :H1839-1846.

[7]Venkatachalam K, Venkatesan B, Valente AJ, et al.WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-alpha (TNF-alpha) -stimulated cardiac fibroblast proliferation but inhibits TNF-alpha-induced cardiomyocyte death[J].J Biol Chem, 2009, 284 (21) :14414-14427.

[8]Pennica D, Swanson TA, Welsh JW, et al.WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors[J].PNAS, 1998, 95 (25) :14717-14722.

[9]Berschneider B, Knigshoff M.WNT1 inducible signaling pathway protein 1 (WISP1) :A novel mediator linking development and disease[J].Int J Biochem Cell Biol, 2011, 43 (3) :306-309.

[10]Jiang F, Parsons CJ, Stefanovic B.Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation[J].J Hepatol, 2006, 45 (3) :401-409.

[11]熊伍军, 何益, 刘菲, 等.Wnt信号通路相关分子在肝纤维化中的表达水平变化及其意义[J].中华消化杂志, 2008, 28 (9) :612-616.

施引文献

资源附件(0)

访问统计