MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism

被引:13
作者
Hsu, Po-Yuan [1 ]
Lin, Wen-Yi [2 ,3 ]
Lin, Ruey-Tay [4 ]
Juo, Suh-Hang H. [1 ,5 ,6 ,7 ,8 ]
机构
[1] China Med Univ Hosp, Dept Med Res, 91 Hsueh Shih Rd, Taichung 40402, Taiwan
[2] Kaohsiung Municipal Hsiaokang Hosp, Dept Occupat Med, Kaohsiung 80708, Taiwan
[3] Kaohsiung Med Univ Hosp, Dept Internal Med, Hepatobiliary Div, Kaohsiung 80708, Taiwan
[4] Kaohsiung Med Univ Hosp, Dept Neurol, Kaohsiung 80708, Taiwan
[5] China Med Univ, Grad Inst Biomed Sci, Taichung 40402, Taiwan
[6] China Med Univ, Inst New Drug Dev, Coll Biopharmaceut & Food Sci, Taichung 40402, Taiwan
[7] China Med Univ, Brain Dis Res Ctr, Taichung 40402, Taiwan
[8] China Med Univ Hosp, Dept Med Res, Ctr Myopia & Eye Dis, Taichung 40402, Taiwan
关键词
microRNA let-7g; lectin-like oxidized low-density lipoprotein receptor-1; cell senescence; angiotensin II; human umbilical vein endothelial cells; insulin-like growth factor; GROWTH-FACTOR-I; CELLULAR SENESCENCE; RECEPTOR; CELLS; LOX-1; ATHEROSCLEROSIS; MUSCLE; PROLIFERATION; CLONING; ACID;
D O I
10.3892/ijmm.2018.3416
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a scavenger receptor that mediates the internalization of oxLDL into cells. Previous studies by our group have indicated that microRNA let-7g exerts an anti-aging effect on ECs and also suppresses LOX-1 expression. Since LOX-1 also induces the aging process, the present study we explored whether let-7g still exerts an anti-aging effect on ECs when LOX-1 is suppressed. Angiotensin II (Ang II) was used to induce senescence in ECs. It was revealed that Ang II significantly increased the expression of aging markers, including -galactosidase, LOX-1, IGF1 and its receptor IGF1R. On the contrary, Ang II decreased the expression of the anti-aging gene sirtuin 1 (SIRT1). When LOX-1 was knocked down by small interfering RNA, let-7g still dose-dependently decreased the expression of -galactosidase (-gal), LOX-1, IGF1 and IGF1R, and SIRT1 was still upregulated. Using senescence-associated -gal staining, it was confirmed that let-7g exerts a LOX-1-independent anti-aging effect on ECs. In conclusion, the present study demonstrated that let-7g has an anti-aging effect regardless of the presence or absence of LOX-1.
引用
收藏
页码:2243 / 2251
页数:9
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