Keratinocyte growth factor induces lipogenesis in alveolar type II cells through a sterol regulatory element binding protein-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 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/EBPdelta. 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 desaturase-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.
Chang
Yongsheng
Y
National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Edeen
Karen
K
Lu
Xiaojun
X
De Leon
Marino
M
Mason
Robert J
RJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005227:Fatty Acids / Q000096:biosynthesis*; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D051780:Sterol Regulatory Element Binding Protein 1; D051523:Fibroblast Growth Factor 7