Published ahead of print on April 6, 2006, doi:10.1165/rcmb.2006-0037OC Am. J. Respir. Cell Mol. Biol., Volume 35, Number 2, August 2006, 268-274 A more recent version of this article appeared on August 1, 2006
Submitted on January 26, 2006 KGF Induces Lipogenesis in Alveolar Type II Cells Through a SREBP-1c Dependent PathwayYongsheng Chang1,1 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA, 2 Center for Molecular Biology and Gene Therapy and Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA * To whom correspondence should be addressed. E-mail: masonb{at}njc.org.
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/EBP
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and C/EBP
. 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.
