2. Academic Validation
  3. Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-β/PI3K/Akt pathway

Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-β/PI3K/Akt pathway

  • Immunol Lett. 2023 May 25;259:1-8. doi: 10.1016/j.imlet.2023.05.009.
Qi-Ming Pang 1,  Qian Zhang 2,  Xiang-Chong Wu 3,  Rui-Lin Yang 4,  Sheng-Ping Fu 3,  Zhen-Hai Fan 4,  Juan Liu 4,  Li-Mei Yu 4,  Jia-Chen Peng 5,  Tao Zhang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China; Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China; Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Human Anatomy, Zunyi Medical University, Zunyi, Guizhou, China.
  • 3 Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 4 Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 5 Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. Electronic address: pengjiachen@139.com.
  • 6 Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China; Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. Electronic address: oceanzt@163.com.
PMID: 37244460 DOI: 10.1016/j.imlet.2023.05.009
Abstract

Recent studies have revealed that activated astrocytes (AS) are divided into two distinct types, termed A1 and A2. A2 astrocytes are neuroprotective and promote tissue repair and regeneration following spinal cord injury. Whereas, the specific mechanism for the formation of the A2 phenotype remains unclear. This study focused on the PI3K/Akt pathway and examined whether TGF-β secreted by M2 macrophages could mediate A2 polarization by activating this pathway. In this study, we revealed that both M2 macrophages and their conditioned medium (M2-CM) could facilitate the secretion of IL-10, IL-13 and TGF-β from AS, and this effect was significantly reversed after the administration of SB431542 (a TGF-β Receptor Inhibitor) or LY294002 (a PI3K Inhibitor). Moreover, immunofluorescence results demonstrated that TGF-β secreted by M2 macrophages could facilitate the expression of A2 biomarker S100A10 in AS; combined with the results of western blot, it was found that this effect was closely related to the activation of PI3K/Akt pathway in AS. In conclusion, TGF-β secreted by M2 macrophages may induce the conversion of AS to the A2 phenotype through the activation of the PI3K/Akt pathway.

Keywords

Astrocyte; Macrophage; Neuroinflammation; Spinal cord injury.

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