Serpina3n in neonatal microglia mediates its protective role for damaged adult microglia by alleviating extracellular matrix remodeling-induced tunneling nanotubes degradation in a cell model of traumatic brain injury.

Autor: Ye G; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Wang Z; Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Pudong New Area, Shanghai 200120, China., Chen P; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Ye J; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Li S; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Chen M; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Feng J; Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China., Wang H; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China., Chen W; Department of Neurosurgery, the Affiliated Lihuili Hospital of Ningbo University. Ningbo 315040, Zhejiang, China; Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Pudong New Area, Shanghai 200120, China. Electronic address: lhlchenwei@nbu.edu.cn.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Nov 28; Vol. 565, pp. 1-9. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1016/j.neuroscience.2024.11.066
Abstrakt: Traumatic brain injury (TBI) induces significant neuroinflammation, primarily driven by microglia. Neonatal microglia (NMG) may have therapeutic potential by modulating the inflammatory response of damaged adult microglia (AMG). This study investigates the influence of NMG on AMG function through extracellular matrix (ECM) remodeling and the formation of tunneling nanotubes (TnTs), with a focus on the role of Serpina3n. We established an in vitro TBI model using a 3D Transwell system, co-culturing damaged AMG with NMG. Viral vector transfection was employed to manipulate Serpina3n expression in NMG. Quantitative real-time PCR, Western blotting, and ELISA were utilized to assess inflammatory markers, ECM remodeling proteins, and TnTs-related proteins. Co-culturing with NMG significantly inhibited M1 polarization of AMG and reduced the release of pro-inflammatory cytokines while promoting M2 polarization and increasing the production of anti-inflammatory cytokines. NMG expressed higher levels of Serpina3n, which played a crucial role in reducing Granzyme B, matrix metalloproteinase (MMP) 2 and MMP9 expression, thereby mitigating ECM remodeling. Inhibition of Serpina3n in NMG increased pro-inflammatory markers and decreased TnTs formation proteins, whereas overexpression of M-sec in AMG counteracted these effects. This highlights the importance of TnTs in maintaining microglial function and promoting an anti-inflammatory environment. In conclusion, NMG improve the function of damaged AMG by modulating ECM remodeling and promoting TnTs formation through the action of Serpina3n.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: