PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase
PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase
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DOI：
10.1002/2211-5463.12194
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发表时间：
2017-03-01
期刊：
影响因子：
2.6
通讯作者：
Demoulin, Jean-Baptiste
中科院分区：
文献类型：
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作者：
de Brachene, Alexandra Coomans;Dif, Nicolas;Demoulin, Jean-Baptiste
硬脂酰辅酶A脱饱和酶(SCD)催化Delta9-顺饱和脂肪酸(SFA)脱饱和生成单不饱和脂肪酸(MUFA)。这种酶在人成纤维细胞中被血小板衍生生长因子(PDGF)高度上调。相应地，细胞脂肪酸的气相色谱分析表明，PDGF显著增加了MUFA在细胞脂中的比例，尤其是棕榈油酸酯。为了进一步分析SCD在成纤维细胞中的作用，我们使用了针对SCD的小发夹RNA(ShSCD)，它降低了MUFA的含量。SCD的下调抑制了PDGF诱导的成纤维细胞的增殖。使用SCD的药理抑制剂证实了这一点。此外，棕榈酸酯和硬脂酸(两种SCD底物)可抑制细胞增殖，但棕榈酸酯和油酸(两种SCD产物)不能阻止细胞增殖。在等量油酸存在的情况下，棕榈酸对细胞增殖没有影响。抑制或下调SCD不会降低PDGF受体的活性或信号转导。然而，通过光漂白后荧光恢复法测量质膜脂质的侧向扩散，我们发现PDGF和SCD抑制剂对MUFA/SFA比率的调节与膜流动性的改变有关。总之，我们的数据表明，SCD是正常成纤维细胞对生长因子做出反应所必需的。
Stearoyl-coenzyme A desaturase (SCD) catalyzes the Delta 9-cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up-regulated by platelet-derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content. SCD down-regulation blunted the proliferation of fibroblasts in response to PDGF. This was confirmed using a pharmacological inhibitor of SCD. In addition, proliferation was blocked by palmitate and stearate (two SCD substrates) but not by palmitoleate and oleate (two SCD products). In the presence of an equal amount of oleate, palmitate had no effect on cell proliferation. SCD inhibition or down-regulation did not decrease PDGF receptor activity or signaling. However, by measuring plasma membrane lipid lateral diffusion by fluorescence recovery after photobleaching, we showed that the modulation of the MUFA/SFA ratio by PDGF and SCD inhibitor was related to modifications of membrane fluidity. Altogether, our data suggest that SCD is required for the response of normal fibroblasts to growth factors.