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Bone marrow mesenchymal stem cells induce M2 microglia polarization through PDGF-AA/MANF signaling
- Source :
- World Journal of Stem Cells
- Publication Year :
- 2020
- Publisher :
- Baishideng Publishing Group Inc, 2020.
-
Abstract
- BACKGROUND Bone marrow mesenchymal stem cells (BMSCs) are capable of shifting the microglia/macrophages phenotype from M1 to M2, contributing to BMSCs-induced brain repair. However, the regulatory mechanism of BMSCs on microglia/macrophages after ischemic stroke is unclear. Recent evidence suggests that mesencephalic astrocyte–derived neurotrophic factor (MANF) and platelet-derived growth factor-AA (PDGF-AA)/MANF signaling regulate M1/M2 macrophage polarization. AIM To investigate whether and how MANF or PDGF-AA/MANF signaling influences BMSCs-mediated M2 polarization. METHODS We identified the secretion of MANF by BMSCs and developed transgenic BMSCs using a targeting small interfering RNA for knockdown of MANF expression. Using a rat middle cerebral artery occlusion (MCAO) model transplanted by BMSCs and BMSCs–microglia Transwell coculture system, the effect of BMSCs-induced downregulation of MANF expression on the phenotype of microglia/macrophages was tested by Western blot, quantitative reverse transcription-polymerase chain reaction, and immunofluorescence. Additionally, microglia were transfected with mimics of miR-30a*, which influenced expression of X-box binding protein (XBP) 1, a key transcription factor that synergized with activating transcription factor 6 (ATF6) to govern MANF expression. We examined the levels of miR-30a*, ATF6, XBP1, and MANF after PDGF-AA treatment in the activated microglia. RESULTS Inhibition of MANF attenuated BMSCs-induced functional recovery and decreased M2 marker production, but increased M1 marker expression in vivo or in vitro. Furthermore, PDGF-AA treatment decreased miR-30a* expression, had no influence on the levels of ATF6, but enhanced expression of both XBP1 and MANF. CONCLUSION BMSCs-mediated MANF paracrine signaling, in particular the PDGF-AA/miR-30a*/XBP1/MANF pathway, synergistically mediates BMSCs-induced M2 polarization.
- Subjects :
- 0301 basic medicine
Histology
biology
Chemistry
Microglia/macrophage polarization
Mesencephalic astrocyte–derived neurotrophic factor
hemic and immune systems
Cell Biology
Basic Study
Bone marrow mesenchymal stem cells
Cerebral ischemia/reperfusion injury
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
stomatognathic system
030220 oncology & carcinogenesis
Genetics
biology.protein
Endoplasmic reticulum stress
Microglia polarization
Bone marrow mesenchymal stem cell
Molecular Biology
Genetics (clinical)
Platelet-derived growth factor receptor
Subjects
Details
- Language :
- English
- ISSN :
- 19480210
- Volume :
- 12
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- World Journal of Stem Cells
- Accession number :
- edsair.doi.dedup.....137972813e67e55e88bb4a31da25a102