Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 4, April, p. 421–430

doi: 10.17219/acem/91826

Publication type: original article

Language: English

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IL-4-polarized BV2 microglia cells promote angiogenesis by secreting exosomes

Yuan Tian1,2,B,C,D, Pei Zhu1,B, Shanshan Liu1,B, Zheng Jin1,B, Dong Li1,E, Heng Zhao3,A, Xun Zhu1,A, Chang Shu4,C, Dongmei Yan1,A,D,E,F, Zehua Dong5,A,F

1 Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China

2 Key Laboratory of Molecular Enzymology and Engineering under the Ministry of Education, College of Life Sciences, Jilin University, Changchun, China

3 Department of Neurosurgery, Stanford University, USA

4 Department of Obstetrics, First Hospital of Jilin University, Changchun, China

5 Intensive Care Unit, the Affiliated Hospital of Qingdao University, China


Background. The microglia cell transfer has been shown to play a protective role in ischemic stroke. Microglia cells may play this nerve-protective role via the promotion of angiogenesis. However, the underlying mechanisms are largely unknown and need further investigation.
Objectives. The aim of this study was to investigate the pro-angiogenesis effects of unpolarized, interleukin-4 (IL-4)-polarized or lipopolysaccharide (LPS)-polarized BV2 microglia cells both in vivo and in vitro. We also investigated the potential mechanisms of these pro-angiogenesis effects.
Material and Methods. BV2 cells were polarized using phosphate-buffered saline (PBS), LPS or IL-4, respectively. The gene expression pattern was analyzed by reverse transcription polymerase chain reaction (RTPCR). The transfer of polarized BV2 cells was performed with an intravenous injection into mice 45 min after the middle cerebral artery (MCA) occlusion. Angiogenin expression was assessed by immunofluorescence. We also examined the angiogenesis effect of polarized BV2 cells and their exosomes through 3-dimensional co-cultures in vitro. Finally, the microRNA (miRNA) profiles of exosomes released by BV2 cells under different polarization conditions were examined using miRNA microarray.
Results. The IL-4-polarized BV2 transplantation promoted angiogenin expression in the ischemic brain. Interleukin-4-polarized microglia increased the tube formation of endothelial cells by secreting exosomes. The miRNA profiles of exosomes released by BV2 cells under different polarization conditions were different. Exosomes from IL-4-polarized BV2 cells contained higher amounts of miRNA-26a compared to those from the LPS-polarized and unpolarized BV2 cells.
Conclusion. Interleukin-4-polarized microglia cells might ameliorate the damage caused by ischemic stroke by promoting angiogenesis through the secretion of exosomes containing miRNA-26a.

Key words

angiogenesis, exosomes, microglia, interleukin-4

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