- 作者：Jian-Feng Wu ; Yan Wang ; Min Zhang ; Yan-Yan Tang ; Bo Wang ; Ping-Ping He ; Yun-Cheng Lv ; Xin-Ping Ouyang ; Feng Yao ; Yu-Lin Tan ; Shi-Lin Tang ; Deng-Pei Tang ; Francisco S. Cayabyab ; Xi-Long Zheng ; Da-Wei Zhang ; Gao-Feng Zeng ; Chao-Ke Tang
- 关键词：GDF-15 ; Cholesterol efflux ; ABCA1 ; Atherosclerosis
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：14 February, 2014
- 年：2014
- 卷：444
- 期：3
- 页码：325-331
- 全文大小：1530 K
Objective
The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase C味 (PKC味)/specificity protein 1 (SP1) pathway in THP-1 macrophages.Methods and results
We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKC味 and SP1, respectively, suggesting the potential roles of PI3K, PKC味 and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKC味 and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation.
Conclusion
Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKC味/SP1 signaling pathway and enhancing cholesterol efflux.