王贺林, 张 玲, 张富洋, 汪 雄, 刘朝中, 陶 凌. GDF11逆转巨噬细胞胆固醇堆积的分子机制研究[J]. 心脏杂志, 2016, 28(5): 503-507.
    引用本文: 王贺林, 张 玲, 张富洋, 汪 雄, 刘朝中, 陶 凌. GDF11逆转巨噬细胞胆固醇堆积的分子机制研究[J]. 心脏杂志, 2016, 28(5): 503-507.
    Effect of GDF11 on cholesterol accumulation in macrophages[J]. Chinese Heart Journal, 2016, 28(5): 503-507.
    Citation: Effect of GDF11 on cholesterol accumulation in macrophages[J]. Chinese Heart Journal, 2016, 28(5): 503-507.

    GDF11逆转巨噬细胞胆固醇堆积的分子机制研究

    Effect of GDF11 on cholesterol accumulation in macrophages

    • 摘要: 目的 观察生长转化因子(GDF)11在巨噬细胞泡沫化中的作用并探讨其可能的分子机制。方法 以不同浓度氧化型低密度脂蛋白(oxLDL)处理RAW264.7细胞,将75 μg/ml oxLDL与不同浓度GDF11共处理过夜,采用荧光染色观察巨噬细胞脂质堆积情况。提取总蛋白或是总RNA,采用Western blot方法检测oxLDL对巨噬细胞GDF11表达的作用,采用实时荧光定量PCR检测GDF11、ABCA1、ABCG1、CD36、IL-1、IL-6及MMP9 mRNA的表达。结果 oxLDL可以显著诱导巨噬细胞胆固醇堆积并抑制巨噬细胞GDF11表达(P<0.05),外源给予GDF11可以抑制oxLDL引起的巨噬细胞胆固醇堆积(P<0.05);oxLDL孵育能够有效诱导CD36、IL-1、IL-6和MMP9 mRNA表达并抑制ABCA1、ABCG1 mRNA表达(P<0.05),外源给予GDF11刺激可以有效逆转oxLDL对于CD36、IL-1、IL-6和MMP9 mRNA的诱导和对于ABCA1、ABCG1 mRNA的抑制(P<0.05)。结论 GDF11可以有效抑制巨噬细胞泡沫化进程,与其有效逆转oxLDL对于CD36、IL-1、IL-6和MMP9 mRNA的诱导和对于ABCA1、ABCG1 mRNA的抑制相关。

       

      Abstract: AIM To investigate the effect of GDF11 on the progression of foam cell formation and to explore the underlying mechanism. METHODSRAW264.7 cells were treated with oxLDL at indicated concentrations or with 75 μg/ml oxLDL and GDF11 at indicated concentrations overnight. Lipid-laden macrophages were detected by immunofluorescent method. Cellular total protein and RNA were extracted. The effect of oxLDL on GDF11 expression was detected by Western blot and the expressions of GDF11, ABCA1, ABCG1, CD36, IL-1, IL-6 and MMP9 mRNA were examined by real-time PCR. RESULTSOxLDL promoted the formation of foam cells and inhibited the expression of GDF11 (P<0.05). However, the exogenous supply of GDF11 inhibited the inducing effect of oxLDL on foam cell formation (P<0.05). oxLDL induced the expression of CD36, IL-1, IL-6 and MMP9 mRNA expressions and inhibited ABCA1 and ABCG1 mRNA expressions (P<0.05). The exogenous supply of GDF11 could reverse the inducing effect of oxLDL on CD36, IL-1, IL-6 and MMP9 mRNA expressions and the inhibitory effect on ABCA1 and ABCG1 mRNA expressions (P<0.05). CONCLUSIONGDF11 can inhibit the progression of foam cell formation induced by oxLDL possibly through its reverse effect on oxLDL-induced CD36, IL-1, IL-6 and MMP9 mRNA expressions and reduction of ABCA1 and ABCG1 mRNA expressions.

       

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