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MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages

Lan, Gang, Xie, Wei, Li, Liang, Zhang, Min, Liu, Dan, Tan, Yu-Lin, Cheng, Hai-Peng, Gong, Duo, Huang, Chong, Zheng, Xi-Long, Yin, Wei-Dong, Tang, Chao-Ke·2016·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2015.10.158
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Abstract

Angiopoietin-like 4 (Angptl4), a secreted protein, is an important regulator to irreversibly inhibit lipoprotein lipase (LPL) activity. Macrophage LPL contributes to foam cell formation via a so-called"molecular bridge" between lipoproteins and receptors on cell surface. It has been reported that macrophage ANGPTL4 suppresses LPL activity, foam cell formation and inflammatory gene expression to reduce atherosclerosis development. Recently, some studies demonstrated that microRNA-134 is upregulated in atherosclerotic macrophages. Here we demonstrate that miR-134 directly binds to 3'UTR of ANGPTL4 mRNA to suppression the expression of ANGPTL4. To investigate the potential roles of macrophage miR-134, THP-1 macrophages were transfected with miR-134 mimics or inhibitors. Our results showed that LPL activity and protein were dramatically increased. We also found that miR-134 activated LPL-mediated lipid accumulation. Collectively, our findings indicate that miR-134 may regulate lipid accumulation and proinfiammatory cytokine secretion in macrophages by targeting the ANGPTL4 gene. Our results have also suggested a promising and potential therapeutic target for atherosclerosis.

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Metadata

Authors
Lan, G., Xie, W., Li, L., Zhang, M., Liu, D., Tan, Y.-L., Cheng, H.-P., Gong, D., Huang, C., Zheng, X.-L., Yin, W.-D., & Tang, C.-K.
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2016-04
Volume
472
Issue
3
Pages
410-417
ISSN
0006-291X
DOI
10.1016/j.bbrc.2015.10.158
Cited by
43
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Funders
  • National Natural Sciences Foundation of China (81270269, 81070220, 81170278)
  • Zhengxiang Scholar Program of University of South China (2014-004)

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