Frontiers in Endocrinology (2019-10-01)

Overexpression of miR-146a Might Regulate Polarization Transitions of BV-2 Cells Induced by High Glucose and Glucose Fluctuations

  • Yinqiong Huang,
  • Zhenling Liao,
  • Xiahong Lin,
  • Xiaohong Wu,
  • Xiaoyu Chen,
  • Xuefeng Bai,
  • Yong Zhuang,
  • Yingxia Yang,
  • Jinying Zhang

DOI
https://doi.org/10.3389/fendo.2019.00719
Journal volume & issue
Vol. 10

Abstract

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Microglia are critical in neuroinflammation. M1/M2 polarization transitions of microglial phenotypes determine the states of neuroinflammation and are regulated by multiple pathways, including miRNAs and other epigenetic regulations. This study investigated the polarization transitions of microglia induced by high glucose and glucose fluctuations, and the role of miR-146a in regulating M1/M2 polarization transitions of microglia. BV-2 cells were cultured with 25 mmol/L glucose, 75 mmol/L glucose, and 25 mmol/L−75 mmol/L glucose fluctuation for 48 h. BV-2 cells overexpressing miR-146a were generated using a lentiviral vector. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure mRNA expression of miR-146a, CD11b, iNOS, Arg-1, IRAK1, TRAF6, and NF-κB. Immunofluorescence was used to measure CD11b expression. Western blot was used to measure protein expression of CD11b, iNOS, and Arg-1. Compared with those in the 25 mmol/L glucose control group, expression of CD11b, iNOS, TNF-α, and IL-6 in the 75 mmol/L glucose or glucose fluctuation groups of cultured BV-2 cells were significantly increased, while Arg-1 and IL-10 was significantly decreased. These effects were reversed by overexpression of miR-146a. Furthermore, expression of IRAK1, TRAF6, and NF-κB was significantly increased in the high glucose and glucose fluctuation groups; this was reduced after miR-146a overexpression. In sum, high glucose and glucose fluctuations induced polarization transitions from M1 to M2 phenotype in BV-2 cells. Overexpression of miR-146a might protect BV-2 cells from high glucose and glucose fluctuation associated with M1/M2 polarization transitions by downregulating the expression of IRAK1, TRAF6, and NF-κB.

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