Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells.
Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells.
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角质形成细胞生长因子和转录因子 C/EBP α、C/EBP δ 和 SREBP-1c 调节 II 型肺泡细胞中的脂肪酸合成。
DOI：
10.1172/jci16793
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Neben,Steven
中科院分区：
文献类型：
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作者：
Mason,RobertJ;Pan,Tianli;Edeen,KarenE;Nielsen,LarryD;Zhang,Feijie;Longphre,Malinda;Eckart,MichaelR;Neben,Steven
刺激内源性表面活性剂产生的策略需要详细了解 II 型肺泡细胞中脂肪生成的调节。我们开发了角质形成细胞生长因子 (KGF) 刺激脂肪酸和磷脂合成的培养条件。 KGF 刺激乙酸盐掺入磷脂酰胆碱、二饱和磷脂酰胆碱和磷脂酰甘油中，仅超过 5% 的大鼠血清。为了确定脂肪生成酶和转运蛋白的 mRNA 水平，我们通过寡核苷酸微阵列分析了基因表达。 KGF 比单独的大鼠血清更能增加脂肪酸合酶、硬脂酰辅酶 A 去饱和酶-1 (SCD-1) 和表皮脂肪酸结合蛋白的 mRNA 水平。 In addition, KGF increased the mRNA levels of the transcription factors CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPδ as well as SREBP-1c (ADD-1), but not PPARγ. C/EBPα 和 C/EBPδ 的这些变化通过原位杂交得到证实。还发现 SCD-1 在体内肺泡 II 型细胞中高表达。此外，KGF 还增加了脂肪酸合酶、C/EBPα、C/EBPδ、SREBP-1、表皮脂肪酸结合蛋白和 SCD 的蛋白质水平。 Finally, the liver X receptor agonist T0901317 increased acetate incorporation and SREBP-1 but not SREBP-2 protein levels.总之，KGF 通过由 C/EBP 同种型和 SREBP-1c 调节的脂肪生成酶和转运蛋白的协调表达来刺激 II 型细胞中的脂肪生成。
Strategies to stimulate endogenous surfactant production require a detailed understanding of the regulation of lipogenesis in alveolar type II cells. We developed culture conditions in which keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis. KGF stimulated acetate incorporation into phosphatidylcholine, disaturated phosphatidylcholin, and phosphatidylglycerol more than 5% rat serum alone. To determine the mRNA levels of lipogenic enzymes and transport proteins, we analyzed gene expression by oligonucleotide microarrays. KGF increased the mRNA levels for fatty acid synthase, stearoyl-CoA desaturase-1 (SCD-1), and epidermal fatty acid–binding protein more than rat serum alone. In addition, KGF increased the mRNA levels of the transcription factors CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPδ as well as SREBP-1c (ADD-1), but not PPARγ. These changes in C/EBPα and C/EBPδ were confirmed by in situ hybridization. SCD-1 was also found to be highly expressed in alveolar type II cells in vivo. Furthermore, KGF increased protein levels of fatty acid synthase, C/EBPα, C/EBPδ, SREBP-1, epidermal fatty acid–binding protein, and SCD. Finally, the liver X receptor agonist T0901317 increased acetate incorporation and SREBP-1 but not SREBP-2 protein levels. In summary, KGF stimulates lipogenesis in type II cells by a coordinated expression of lipogenic enzymes and transport proteins regulated by C/EBP isoforms and SREBP-1c.