Keratinocyte Growth Factor Induces Lipogenesis in Alveolar Type II Cells through a Sterol Regulatory Element Binding Protein-1c–Dependent Pathway
- 1 August 2006
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 35 (2), 268-274
- https://doi.org/10.1165/rcmb.2006-0037oc
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cellsJournal of Lipid Research, 2005
- Glucose induces de novo lipogenesis in rat muscle satellite cells through a sterol-regulatory-element-binding-protein-1c-dependent pathwayJournal of Cell Science, 2004
- New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1cBiochemical Journal, 2002
- Insulin and Sterol-regulatory Element-binding Protein-1c (SREBP-1C) Regulation of Gene Expression in 3T3-L1 AdipocytesPublished by Elsevier BV ,2002
- ADD1/SREBP-1c Mediates Insulin-Induced Gene Expression Linked to the MAP Kinase PathwayBiochemical and Biophysical Research Communications, 1998
- Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma.JCI Insight, 1998
- Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.JCI Insight, 1998
- Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells.JCI Insight, 1997
- ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.Genes & Development, 1996
- Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium.JCI Insight, 1993