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Published ahead of print on April 6, 2006, doi:10.1165/rcmb.2006-0037OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 35, pp. 268-274, 2006
© 2006 American Thoracic Society
DOI: 10.1165/rcmb.2006-0037OC

Keratinocyte Growth Factor Induces Lipogenesis in Alveolar Type II Cells through a Sterol Regulatory Element Binding Protein-1c–Dependent Pathway

Yongsheng Chang, Karen Edeen, Xiaojun Lu, Marino De Leon and Robert J. Mason

Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; and Center for Molecular Biology and Gene Therapy and Department of Physiology, Loma Linda University School of Medicine, Loma Linda, California

Correspondence and requests for reprints should be addressed to Robert J. Mason, M.D., National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. 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 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/EBP{delta}. 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.

Key Words: adenovirus • fatty acid synthesis • surfactant




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