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Role of Keratinocyte Growth Factor in Regulating Lipogenesis in Alveolar Type II Cells*: A Gene-Profiling Approach FREE TO VIEW

Robert J. Mason, MD; Bifeng Gao, PhD; Tianli Pan, MD; Xiaoqiao Jiang, BS; Michael Eckart, PhD; Steven Neben, PhD
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*From the Department of Medicine (Drs. Mason and Pan), National Jewish Medical and Research Center, Denver, CO; University of Colorado Health Sciences Center (Dr. Gao); Denver, CO; and Bayer Corporation (Drs. Eckart and Neben, and Mr. Jiang), Berkeley, CA.

Correspondence to: Robert J. Mason, MD, National Jewish Medical and Research Center, Department of Medicine, 1400 Jackson St, Denver, CO 80206; e-mail: masonb@njc.org

Chest. 2002;121(3_suppl):77S. doi:10.1378/chest.121.3_suppl.77S
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Keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of alveolar type II cells in vitro. To define the genes that are activated in this process, we analyzed messenger RNA from type II cells that had been cultured in the presence and absence of KGF by DNA microarray analysis with a gene profiling system (Affymetrix; Santa Clara, CA). The first experiment was a time course comparing KGF-treated cultures and untreated cultures at 1, 3, 8, and 24 h (n = 2). The second experiment was to access differentiation after 6 days with and without KGF treatment (n = 3). We used acetate labeling to demonstrate lipogenesis. KGF stimulated acetate incorporation into desaturated phosphatidylcholine (38-fold). By microarray analyses, KGF increased the expression of two transcription factors (CCAT enhancer binding protein [C/EBP-α] [8.1-fold] and sterol regulatory element-binding protein [SREBP]/ADD1 [9.7-fold]) and several lipogenic proteins (fatty acid synthase [4.7-fold], stearyl-coenzyme A desaturase [26.3-fold], and epidermal fatty acid binding protein [7.9-fold]). These results were independently verified by real-time polymerase chain reaction for all the genes and for fatty acid synthase, C/EBP-α, and SREBP-1c/ADD1 by Western blot analysis. We concluded that KGF increases lipogenesis in type II cells in vitro by the activation of C/EBP-α and SREBP-1c/ADD1.

Abbreviations: C/EBP = CCAAT enhancer binding protein; KGF = keratinocyte growth factor; SREBP = sterol regulatory element-binding protein




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