TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro
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.
KeywordsTGF-β Spinal cord injury Astrocyte M2 macrophage Glial scar Neurocan
This work was supported by grants from Tackle Key Problems in Science and Technology of Guizhou Province (No. SY  3119) and the Project for Academic Seedling Cultivation and Innovation Exploration of Zunyi Medical University (No.  5733-029).
- da Silva Alves E, de Aquino Lemos V, Ruiz da Silva F et al (2013) Low-grade inflammation and spinal cord injury: exercise as therapy? Mediat Inflamm 2013:971841Google Scholar
- Hara M, Kobayakawa K, Ohkawa Y, Kumamaru H, Yokota K, Saito T, Kijima K, Yoshizaki S, Harimaya K, Nakashima Y, Okada S (2017) Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury. Nat Med 23(7):818–828CrossRefGoogle Scholar
- Weischenfeldt J, Porse B (2008) Bone marrow-derived macrophages (BMM): isolation and applications. CSH Protoc 2008(12):pdb.prot5080Google Scholar