Article

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

The Jake Gittlen Cancer Research Foundation, Hershey, Pennsylvania, USA.
Journal of Investigative Dermatology (Impact Factor: 6.19). 06/2008; 128(5):1286-93. DOI: 10.1038/sj.jid.5701155
Source: PubMed

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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