IGF-1 Induces SREBP-1 Expression and Lipogenesis in SEB-1 Sebocytes via Activation of the Phosphoinositide 3-Kinase/Akt Pathway

Understanding the factors that regulate sebum production is important in identifying therapeutic targets for acne therapy. Insulin and IGF-1 stimulate sebaceous gland lipogenesis. IGF-1 increases expression of sterol response element-binding protein-1 (SREBP-1), a transcription factor that regulates...

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Bibliographic Details
Published in:Journal of investigative dermatology 2008-05, Vol.128 (5), p.1286-1293
Main Authors: Smith, Terry M., Gilliland, Kathryn, Clawson, Gary A., Thiboutot, Diane
Format: Article
Language:English
Subjects:
Acne Vulgaris - metabolism
Biological and medical sciences
Cell Line, Transformed
Chromones - pharmacology
Dermatology
Enzyme Inhibitors - pharmacology
Extracellular Signal-Regulated MAP Kinases - metabolism
Flavonoids - pharmacology
Gene Expression - drug effects
Gene Expression - physiology
Humans
Insulin-Like Growth Factor I - drug effects
Insulin-Like Growth Factor I - metabolism
JNK Mitogen-Activated Protein Kinases - metabolism
Lipogenesis - drug effects
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Medical sciences
Morpholines - pharmacology
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Sebaceous Glands - cytology
Sebaceous Glands - enzymology
Sebum - metabolism
Sterol Regulatory Element Binding Protein 1 - genetics
Sterol Regulatory Element Binding Protein 1 - metabolism
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Summary:Understanding the factors that regulate sebum production is important in identifying therapeutic targets for acne therapy. Insulin and IGF-1 stimulate sebaceous gland lipogenesis. IGF-1 increases expression of sterol response element-binding protein-1 (SREBP-1), a transcription factor that regulates numerous genes involved in lipid biosynthesis. SREBP-1 expression, in turn, stimulates lipogenesis in sebocytes. The goal of this study was to identify the intracellular signaling pathway(s) that transduces the lipogenic signal initiated by IGF-1. Sebocytes were treated with IGF-1 and assayed for activation of the phosphoinositide 3-kinase (PI3-K) pathway and of the three major arms of the mitogen-activated protein kinase (MAPK) pathway (MAPK/extracellular signal-regulated kinase (ERK), p38 MAPK, and stress-activated protein kinase/c-Jun-N terminal kinase). IGF-1 activated the MAPK/ERK and PI-3K pathways. Using specific inhibitors of each pathway, we found that the increase in expression of SREBP-1 induced by IGF-1 was blocked in the presence of the PI3-K inhibitor but not in the presence of the MAPK/ERK inhibitor. Furthermore, inhibition of the PI3-K pathway also blocked the IGF-1-induced transcription of SREBP target genes and sebocyte lipogenesis. These data indicate that IGF-1 transmits its lipogenic signal in sebocytes through activation of Akt. Specific targeted interruption of this pathway in the sebaceous gland could be a desirable approach to reducing sebum production and improving acne.
ISSN:0022-202X
1523-1747
DOI:10.1038/sj.jid.5701155