KGF induces lipogenesis in alveolar type II cells through a SREBP-1c dependent pathway

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 stearoyl-CoA desaturase-1 and transcription factors involved in lipogenesis such as SREBP-1c and C/EBPα and C/EBPδ. 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 FAS and SCD-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-1c 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.