4.5 Article

MicroRNA-21, induced by high glucose, modulates macrophage apoptosis via programmed cell death 4

Journal

MOLECULAR MEDICINE REPORTS
Volume 12, Issue 1, Pages 463-469

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.3398

Keywords

microRNA-21; programmed cell death 4; macrophage; apoptosis; high glucose; atherosclerosis

Funding

  1. National Basic Research Program of China (973 program) [2012CB722406]
  2. National Natural Science Foundation of China [30971215, 81070192, 81070141, 81100605, 81270352, 81270287]
  3. Natural Science Foundation of Shandong Province [BS2011YY013, BS2013YY017]
  4. Independent Innovation Foundation of Shandong University [2012JC034]
  5. Cardiovascular Exploration Research Foundation of the Chinese Medical Doctors Association [DFCMDA201320]

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MicroRNA-21 (miR-21) has been found to promote cell proliferation and survival. It has also been shown to exhibit an increased expression in a number of forms of cardiovascular disease. However, the mechanisms underlying the involvement of miR-21 in atherosclerosis remain to be elucidated. In the present study, it was demonstrated that miR-21 was upregulated in a time-dependent manner in response to high-concentration glucose stimulation in Raw 264.7 macrophages. High concentrations of glucose induce macrophage apoptosis. miR-21-inhibited macrophages treated with a normal concentration of glucose exhibited increased levels of cell apoptosis and augmented levels of activated caspase-3, while cells treated with an miR-21 inhibitor and a high concentration of glucose, revealed significantly increased levels of apoptosis. In addition, inhibition of miR-21 increased mRNA and protein levels of programmed cell death 4 (PDCD4), which, by contrast, were reduced in miR-21-inhibited cells that had been treated with a high concentration of glucose. In conclusion, miR-21 is sensitive to high-concentration glucose treatment in macrophages, and appears to have a protective effect in macrophage apoptosis induced by high concentrations of glucose via PDCD4.

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