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TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro

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Abstract

Transforming growth factor-β (TGF-β) is a key factor that promotes fibrosis or scar formation, which could become an obstacle in the repair of impaired axons in the central nervous system (CNS) of the human body resulting from diseases or injuries. Considering that major pathological reactions occur during this process, we focused on TGF-secreting M2 macrophages to identify the interactions between M2 macrophages and astrocytes (AS) and verify the specific mechanism of fibrosis or glial scar formation. In the present study, we used the Transwell coculturing technique and found an increase in glial fibrillary acidic protein (GFAP), neurocan, IL-13, and TGF-β expression after incubation for 48 h; the expression of these proteins decreased when additional inhibitors of the TGF-β receptor were added. We concluded that fibrosis or glial scar formation would be enhanced by the secretion of neurocan from AS, resulting from the release of TGF-β from M2 macrophages. We also used M2 macrophage–conditioned medium to further confirm this finding in a subsequent experiment. We hope that the findings in this research could provide a foundation for locating new targets for treating CNS diseases or injuries.

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Funding

This work was supported by grants from Tackle Key Problems in Science and Technology of Guizhou Province (No. SY [2012] 3119) and the Project for Academic Seedling Cultivation and Innovation Exploration of Zunyi Medical University (No. [2017] 5733-029).

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Authors and Affiliations

  1. Department of Human Anatomy, Zunyi Medical University, Zunyi, Guizhou, China

    Gongyu Song, Qian Zhang & Changpei Yang

  2. Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Center, Affiliated Hospital of Zunyi Medical University, 149 Dalian Rd., Zunyi, 563000, Guizhou, China

    Rui Yang & Tao Zhang

  3. Experimental Medical Centre, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, China

    Long Chen

  4. Department of Physiology, Zunyi Medical University, Zunyi, Guizhou, China

    Dujuan Huang & Junwei Zeng

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  1. Gongyu Song
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  2. Rui Yang
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  3. Qian Zhang
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  4. Long Chen
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  5. Dujuan Huang
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  7. Changpei Yang
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  8. Tao Zhang
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Correspondence to Qian Zhang or Tao Zhang.

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Gongyu Song and Rui Yang are co-first authors.

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Song, G., Yang, R., Zhang, Q. et al. TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro. J Mol Neurosci 69, 324–332 (2019). https://doi.org/10.1007/s12031-019-01361-5

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  • DOI: https://doi.org/10.1007/s12031-019-01361-5

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