Keratinocyte growth factor induces lipogenesis in alveolar type II cells through a sterol regulatory element binding protein-1c-dependent pathway
Keratinocyte growth factor induces lipogenesis in alveolar type II cells through a sterol regulatory element binding protein-1c-dependent pathway
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DOI：
10.1165/rcmb.2006-0037oc
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发表时间：
2006-08-01
影响因子：
6.4
通讯作者：
Mason, Robert J.
中科院分区：
文献类型：
--
作者：
Chang, Yongsheng;Edeen, Karen;Mason, Robert J.
角质细胞生长因子（KGF）刺激肺泡II型细胞脂肪酸和磷脂合成的体外研究。KGF刺激脂肪生成酶，包括脂肪酸合成酶和硬脂酰辅酶A去饱和酶-1，以及参与脂肪生成的转录因子，如固醇调节元件结合蛋白（SREBP）-1c和CCAAT/增强子结合蛋白（C/EBP）α和C/EBP 8。为了确定SREBP-1c在诱导大鼠II型细胞原代培养物中脂肪生成基因和KGF脂肪生成中的作用，我们使用腺病毒载体来改变SREBP-1c的水平。过表达显性负性形式的SREBP-1减少脂肪生成，并减少KGF对脂肪酸合成酶和硬脂酰辅酶A clesaturase-1的诱导。相反，腺病毒介导的SREBP-1c组成型活性形式的过表达模拟了KGF对脂肪生成酶和脂肪生成的作用。这些数据表明，SREBP-1c是肺泡II型细胞中KGF刺激脂肪生成所必需的，并且是肺脂质代谢的关键调节因子，并且SREBP-1c的表达足以诱导大鼠II型细胞中的脂肪生成。
Keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis in alveolar type II cells in vitro. KGF stimulates lipogenic enzymes, including fatty acid synthase and stearyl-CoA desaturase-1, and transcription factors involved in lipogenesis, such as sterol regulatory element binding protein (SREBP)-1c and CCAAT/enhancer binding protein (C/EBP)alpha and C/EBP8. To define the role of SREBP-1c on the induction of lipogenic genes and lipogenesis by KGF in primary cultures of rat type II cells, we used adenoviral vectors to alter levels of SREBP-1c. Overexpression of a dominant-negative form of SREBP-1 decreased lipogenesis and decreased the induction of fatty acid synthase and stearyl coenzyme A clesaturase-1 by KGF. Conversely, adenovirus-mediated overexpression of a constitutively active form of SREBP-1c mimicked the effect of KGF on lipogenic enzymes and lipogenesis. These data indicate that SREBP-1 c is required for the stimulation of lipogenesis by KGF in the alveolar type II cells and is a key regulator of lung lipid metabolism and that expression of SREBP-1c is sufficient to induce lipogenesis in rat type II cells.