表皮生长因子及其受体在多囊肾病大鼠体液及肾组织中的表达及意义
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国家自然科学基金重点项目(30330640),国家自然科学基金(30170901),国家科技部重大科技专项基金(2002AA2Z3130).


Expression of EGF/EGFR in body fluids and kidney tissues of rats with polycystic kidney disease and its significance
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Supported by the Key Program of National Natural Science Foundation of China(30330640),National Natural Science Foundation of China(30170901) and the grant from the National Sciences and Technologies R&D Program (2002AA2Z3130).

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    摘要:

    目的:观察常染色体显性多囊肾病大鼠体液及肾脏组织中表皮生长因子(EGF)及其受体(EGFR)的表达,探讨二者在多囊肾病发病过程中的作用。方法:采用ELISA方法检测多囊肾病Han:SPRD大鼠血液、尿液中EGF含量,蛋白质印迹法、原位杂交及免疫组织化学方法观察EGF/EGFR在大鼠肾组织的表达。结果:大鼠尿液中EGF含量远高于血液,3周龄大鼠体液EGF含量高于3个月龄,杂合患病大鼠尿液中EGF浓度(pg/ml)显著低于正常大鼠(263.45±48.53 vs 321.09±74.57,P<0.05)。患病大鼠肾组织EGF表达位置不变,但表达量显著低于正常;EGFR异位表达在囊肿细胞基底膜面和腔膜面,且表达强于正常大鼠;EGFR与磷酸化EGFR表达量从高至低依次为cy/cy大鼠、cy/+大鼠和+/+大鼠。结论:多囊肾病大鼠发病过程中存在EGF/EGFR信号转导通路的异常激活。

    Abstract:

    Objective:To observe the expression of epidermal growth factor (EGF) and its receptor (EGFR) in the body fluids and renal tissues of rats with autosomal dominant polycystic kidney disease (ADPKD) and to explore their roles in the development of the disease.Methods:EGF levels in the blood and urine of Han:SPRD rats were determined by ELISA. Western blotting,in situ hybridization and immunohistochemistry were used to examine the expression of EGF/EGFR in the kidneys of ADPKD rats. Results:The concentration of EGF in the urine was higher than that in the blood. EGF level in the body fluids of 3 weeks old rats was higher than that of the 3 months old rats. The urine EGF level of cy/+ rats was significantly lower than that in the normal rats (\[263.45±48.53\] pg/ml vs \[321.09±74.57\] pg/ml,P<0.05). The renal distribution pattern of EGF remained unchanged in rats with ADPKD,but the expression level was down-regulated. EGFR in ADPKD rats was ectopically overexpressed on the apical and basolateral membrane of cystic cells. The order of EGFR and phosphorylated EGFR expression was: cy/cy rat> cy/+ rat> +/+rat.Conclusion:The abnormal EGF/EGFR might play a key role in the development and progression of the ADPKD.

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  • 收稿日期:2008-10-13
  • 最后修改日期:2008-11-13
  • 录用日期:2008-12-02
  • 在线发布日期: 2009-01-16
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