福克斯O1
内分泌学
内科学
PI3K/AKT/mTOR通路
蛋白激酶B
胰岛素样生长因子
胰岛素
生物
磷酸肌醇3激酶
胰岛素受体
生长因子
转录因子
脂肪生成
化学
LY294002型
细胞生物学
信号转导
胰岛素抵抗
脂质代谢
受体
生物化学
医学
基因
作者
Yasaman Mirdamadi,Anja Thielitz,Antje Wiede,Alexander Goihl,Eleni Papakonstantinou,Roland Hartig,Christos C. Zouboulis,Dirk Reinhold,Luca Simeoni,Ursula Bommhardt,Sven Quist,Harald Gollnick
标识
DOI:10.1016/j.mce.2015.08.001
摘要
A recent hypothesis suggests that a high glycaemic load diet-associated increase of insulin-like growth factor-1 (IGF-1) and insulin may promote acne by reducing nuclear localization of the forkhead box-O1 (FoxO1) transcription factor via activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. Using SZ95 sebocytes as a model, we investigated the effect of the most important insulinotropic western dietary factors, IGF-1 and insulin on acne. SZ95 sebocytes were stimulated with different concentrations of IGF-1 and insulin (0.001, 0.01, 0.1 and 1 μM) for 15 to 120 min ± PI3K inhibitor LY294002 (50 μM). Cytoplasmic and nuclear protein expression of p-Akt and p-FoxO1 as well as FoxO transcriptional activity was analysed. In addition, the proliferation and differentiation of sebocytes and their TLR2/4 expression were determined. We found that high concentrations of IGF-1 and insulin differentially stimulate the PI3K/Akt/FoxO1 pathway by an early up-regulation of cytoplasmic p-Akt and delayed up-regulation of p-FoxO1 resulting in FoxO1 shift to the cytoplasm and the reduction of FoxO transcriptional activity, physiological serum concentration had no effect. IGF-1 at concentrations of 0.1 and 1 μM significantly reduced proliferation but increased differentiation of sebocytes to a greater extent than insulin (0.1 and 1 μM), but up-regulated TLR2/4 expression to comparable extent. These data provide the first in vitro evidence that FoxO1 principally might be involved in the regulation of growth-factor-stimulatory effects on sebaceous lipogenesis and inflammation in the pathological condition of acne. However, the in vivo significance under physiological conditions remains to be elucidated.
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