E₂ - BSA activates caveolin-1 via PI₃K/ERK1/2 and lysosomal degradation pathway and contributes to EPC proliferation

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• 作者：Zhi Tan^a ; ^{tanzhi@mail.sysu.edu.cn} ; Li-Jun Zhou^a ; Yu Li^b ; Yu-Hong Cui^a ; Qiu-Ling Xiang^a ; Gui-Ping Lin^a ; Ting-Huai Wang^a ; ^{tinghuaiwang@yahoo.com}
• 关键词：Endothelial progenitor cell ; Estrogen ; Estrogen receptor ; Caveolae ; Caveolin-1
• 刊名：International Journal of Cardiology
• 出版年：2012
• 期刊代码：128_01675273
• 类别：med
• 出版时间：28 June, 2012
• 卷：158
• 期：1
• 页码：46-53
• 文件大小：983 K

摘要

Background

The mechanism that estrogen (E₂) increases the number of endothelial progenitor cells (EPC) is largely unknown. Here we used E₂-conjugated bovine serum albumin (E₂-BSA, membrane impermeable) to investigate whether the membrane estrogen receptor (mER) and its related protein caveolin-1 (CAV-1) are involved in these processes.

Methods and results

E₂-BSA promoted [³H]-thymidine incorporation of EPC through increasing CAV-1 expression via mER (ER伪, but not ER尾 or GPR30). Both cholesterol depletion and CAV-1 knockdown with use of CAV-1 siRNA significantly attenuated E₂-BSA-induced [³H]-thymidine incorporation. Western blot showed that E₂-BSA increased membrane CAV-1 protein expression聽12 h after treatment, whereas mRNA levels of CAV-1 were augmented until 24 h after E₂-BSA treatment. Furthermore, pre-incubated EPC with ICI 182780 (a specific ER antagonist), LY 294002 (a selective PI₃K inhibitor) or PD 98059 (a specific ERK1/2 inhibitor) before E₂-BSA inhibited the late-stage effect of E₂-BSA (鈮?#xA0;24 h) on up-regulation of CAV-1 mRNA and protein expression. Pulse chase results demonstrated that E₂-BSA inhibited lysosome-mediated degradation of CAV-1 protein at the early stage (鈮?#xA0;12 h), and then resulted in the increased CAV-1 protein.

Conclusion

In the present work we demonstrated that E₂-BSA promotes EPC proliferation through mER锛圗R伪锛塱n CAV-1-dependent manner: prolonging the stability of CAV-1 protein through quick inhibition of the lysosomal degradation pathway at the early stage (鈮?#xA0;12 h) and up-regulating CAV-1 at transcription levels through PI₃K/ERK1/2 signaling pathway at the late stage (鈮?#xA0;24 h). These data indicated that a there is a novel mechanism of E₂-BSA in the regulation of EPC proliferation through CAV-1.