Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKC&alpha;/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells | Zendy

Xin Zhang | Zendy; Qiong Ye | Zendy; Duo Gong | Zendy; Yuan Lv | Zendy; Haipeng Cheng | Zendy; Chong Huang | Zendy; Lingyan Chen | Zendy; Zhen-Wang Zhao | Zendy; Liang Li | Zendy; Wei Xie | Zendy; Min Zhang | Zendy; Xiao-Dan Xia | Zendy; Xiaohua Yu | Zendy; XiLong Zheng | Zendy; Shuzhi Wang | Zendy; Zongbao Wang | Zendy; ChaoKe Tang | Zendy

Open Access

Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells

Author(s) -

Xin Zhang,

Qiong Ye,

Duo Gong,

Yuan Lv,

Haipeng Cheng,

Chong Huang,

Lingyan Chen,

Zhen-Wang Zhao,

Liang Li,

Wei Xie,

Min Zhang,

Xiao-Dan Xia,

Xiaohua Yu,

XiLong Zheng,

Shuzhi Wang,

Zongbao Wang,

ChaoKe Tang

Publication year - 2017

Publication title -

acta biochimica et biophysica sinica

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.771

H-Index - 57

eISSN - 1745-7270

pISSN - 1672-9145

DOI - 10.1093/abbs/gmx038

Subject(s) - apelin , lipoprotein lipase , inflammation , western blot , tumor necrosis factor alpha , cytokine , chemistry , protein kinase c , signal transduction , endocrinology , macrophage , medicine , microbiology and biotechnology , biology , adipose tissue , biochemistry , receptor , gene , in vitro

Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.

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