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Astrocyte-derived lipocalin 2 promotes inflammation and scarring after spinal cord injury by activating SMAD in mice.

Authors :
Wang X
Zhu Z
Zhang Z
Liang Z
Li K
Ma Y
Zhou J
Wu T
Wang Z
Hu X
Source :
Experimental neurology [Exp Neurol] 2024 Oct; Vol. 380, pp. 114915. Date of Electronic Publication: 2024 Aug 07.
Publication Year :
2024

Abstract

Background: The inflammatory response and scar formation after spinal cord injury (SCI) limit nerve regeneration and functional recovery. Our research group has previously shown that the expression of astrocyte-derived lipocalin 2 (Lcn2) is upregulated after SCI, which correlates with neuronal apoptosis and functional recovery. Therefore, we speculate that astrocyte-specific knockdown of Lcn2 after SCI may lead to a better prognosis.<br />Methods: Tissue RNA sequencing, Western blotting, PCR, and immunofluorescence assays were conducted to assess the expression of Lcn2 following SCI in mice. Adeno-associated virus 9 (AAV9) transfection was employed to specifically reduce the expression of Lcn2 in astrocytes, and subsequent evaluations of scarring and inflammation were conducted. In vitro experiments involved treating primary astrocytes with TGF-β or an A1-induced mixture (C1q, TNF-α and IL-1α) following Lcn2 knockdown. Finally, the intrathecal injection of recombinant Lcn2 (ReLcn2) protein was conducted post-injury to further confirm the role of Lcn2 and its underlying mechanism in SCI.<br />Results: Lcn2 expression was elevated in astrocytes after SCI at 7 dpi (days post injury). Lcn2 knockdown in astrocytes is beneficial for neuronal survival and functional recovery after SCI, and is accompanied by a reduced inflammatory response and inhibited scar formation. The inhibition of SMAD-associated signaling activation was identified as a possible mechanism, and in vitro experiments further confirmed this finding. ReLcn2 further activated SMAD-associated signaling and aggravated motor function after SCI.<br />Conclusion: The upregulation of Lcn2 expression in astrocytes is involved in neuroinflammation and scar formation after SCI, and the activation of SMAD-associated signaling is one of the underlying mechanisms.<br />Competing Interests: Declaration of competing interest All authors consent to this article for publication. The authors declare that they have no competing interests.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2430
Volume :
380
Database :
MEDLINE
Journal :
Experimental neurology
Publication Type :
Academic Journal
Accession number :
39122167
Full Text :
https://doi.org/10.1016/j.expneurol.2024.114915