脂氧素A4拮抗CTGF所致的人肾小管上皮细胞转分化
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国家自然科学基金资助项目(30871180)


Lipoxin A4 inhibits epithelial-myofibroblast transdifferentiation of human renal tubular epithelial cells induced by CTGF
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    摘要:

    目的:探讨脂氧素A4(LXA4)对结缔组织生长因子(CTGF)诱导的肾小管上皮细胞HK2转分化的影响-方法:在体外培养的人肾小管上皮细胞(HK2细胞)中,加入CTGF和LXA4刺激48 h后,用倒置显微镜观察细胞形态学变化,应用RT-PCR-Western blot方法测定上皮细胞E钙黏蛋白和α-平滑肌肌动蛋白(α-SMA)mRNA与蛋白的表达-结果:CTGF刺激使HK2细胞形态由椭圆形转为梭形,下调E钙黏蛋白mRNA与蛋白表达,上调α-SMA的mRNA与蛋白表达-LXA4能够抑制CTGF所致的上述变化,E钙黏蛋白mRNA与蛋白的相对表达值分别为0.270 ± 0.082和0.827 ± 0.177,分别高于CTGF刺激组的0.067 ± 0.015(P < 0.05)和0.257 ± 0.221(P < 0.05);α-SMA的mRNA与蛋白表达的相对表达值分别为0.070±0.046和0.023±0.023,分别低于CTGF刺激组的0.653 ± 0.256(P < 0.05)和0.167 ± 0.050(P < 0.05)-结论:外源性CTGF能导致HK2细胞转分化为肌成纤维细胞,LXA4可抑制CTGF对HK2细胞的转分化,这为治疗肾间质纤维化提供了一条新途径-

    Abstract:

    Objective:To investigate the effects of lipoxin A4(LXA4)on epithelial- myofibroblast transdifferentiation(EMT)induced by recombinant human connective tissue growth factor(CTGF)in human renal tubular epithelial cell line(HK2)in vitro. Methods:The cultured HK2 cells were stimulated with CTGF for 48 hours with or without pretreatment of LXA4. The morphological changes were observed under an inverted microscope. The expressions of E-cadherin,α-smooth muscle actin(α-SMA)were detected by RT-PCR and Western blot. Results:CTGF induced the morphological changes of HK2 cells from oval to fusiform and stellate appearance,down-regulated the E-cadherin expression and up-regulated α-SMA expression both on mRNA and protein level. The expressions of mRNA and protein of E-cadherin reduced by CTGF(0.067 ± 0.015 and 0.257 ± 0.221,respectively)were increased by LXA4(0.270 ± 0.082 and 0.827 ± 0.177 respectively,P < 0.05). The expressions of mRNA and protein of α-SMA stimulated by CTGF(0.653 ± 0.256 and 0.167 ± 0.050,respectively)were inhibited by LXA4(0.070 ± 0.046 and 0.023 ± 0.023,respectively,P < 0.05). Conclusion:LXA4 inhibited the EMT of HK2 cells induced by CTGF. It suggests that the inhibition of LXA4 on CTGF-induced EMT could be a therapeutic strategy against tubulointerstitial fibrosis.

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张永梅,吴升华,陆 超,任 伟,陶慧娴.脂氧素A4拮抗CTGF所致的人肾小管上皮细胞转分化[J].南京医科大学学报(自然科学版),2009,29(7):925-929

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