脂氧素A4抑制结缔组织生长因子诱导的肾小管上皮细胞表达整合素连接激酶
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国家自然科学基金资助项目(30871180)


Inhibition of CTGF-induced expression of integrin-linked kinase by lipoxin A4 in human renal tubular epithelial cells
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    摘要:

    目的:结缔组织生长因子(connective tissue growth factor,CTGF)可诱导人肾小管上皮细胞HK-2表达整合素连接激酶(integrin-linked kinase,ILK),本研究观察脂氧素A4(lipoxin A4,LXA4)是否调节CTGF对合成ILK的作用,并探讨其作用机制-方法:对体外培养的人肾小管上皮细胞(HK-2细胞株),用不同浓度的LXA4预刺激,再加入CTGF共同孵育;或单用CTGF刺激HK-2细胞-应用RT-PCR和Western blot方法测定ILK mRNA和蛋白表达,应用Western blot法测定分裂原激活的蛋白激酶(p42/44 mitogen-activated protein kinase,p42/44 MAPK)(也称为ERK1/2)-磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3-K)-结果:CTGF刺激使HK-2细胞ILK mRNA表达和蛋白合成增加,磷酸化ERK1/2-磷酸化PI3-K的表达增加-LXA4呈剂量依赖性地抑制CTGF所致的上述变化-结论:LXA4可抑制CTGF引起的HK-2细胞表达ILK,其机制依赖于抑制ERK1/2-PI3-K的磷酸化-

    Abstract:

    Objective:Connective tissue growth factor(CTGF) can induce the expression of integrin-linked kinase(ILK)in human renal tubular epithelial cell line(HK-2). In this study,we investigated the modulatory effect of lipoxin A4(LXA4)on action of CTGF-induced ILK expression,and explored the mechanisms of the action of LXA4. Methods:Cultured HK-2 cells were stimulated with CTGF with or without pretreatment of LXA4. The expression of ILK mRNA was detected by RT-PCR. The expressions of ILK protein,p42/P44 mitogen-activated protein kinase(p42/44 MAPK)(also called ERK1/2) and phosphoinositide 3-kinase(PI3-K) were detected by western blot. Results:CTGF up-regulated the mRNA and protein expressions of ILK,and up-regulated the expression of phospho-ERK1/2 and phospho-PI3-K. LXA4 dose-dependently inhibited the above action of CTGF. Conclusion:LXA4 inhibits CTGF-induced expression of ILK via ERK1/2 and PI3-K-dependent signal pathway.

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陶慧娴,吴升华.脂氧素A4抑制结缔组织生长因子诱导的肾小管上皮细胞表达整合素连接激酶[J].南京医科大学学报(自然科学版),2010,(5):586-590

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  • 收稿日期:2009-12-06
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