IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway

Terry M. Smith, Kathryn Gilliland, Gary A. Clawson, Diane Thiboutot

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1286-1293
Number of pages8
JournalJournal of Investigative Dermatology
Volume128
Issue number5
DOIs
StatePublished - Jan 1 2008

Fingerprint

Lipogenesis
1-Phosphatidylinositol 4-Kinase
Response Elements
Sterols
Phosphatidylinositols
Insulin-Like Growth Factor I
Carrier Proteins
Phosphotransferases
Chemical activation
Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Sebum
Sebaceous Glands
Acne Vulgaris
Genes
JNK Mitogen-Activated Protein Kinases
Biosynthesis
p38 Mitogen-Activated Protein Kinases
Transcription
Heat-Shock Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

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abstract = "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.",
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IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. / Smith, Terry M.; Gilliland, Kathryn; Clawson, Gary A.; Thiboutot, Diane.

In: Journal of Investigative Dermatology, Vol. 128, No. 5, 01.01.2008, p. 1286-1293.

Research output: Contribution to journalArticle

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