TITLE:
SIRT1 Regulates Autophagy and Activation of Microglia through Smad3/TRIB3 Signaling Axis to Improve Spinal Cord Injury
AUTHORS:
Li Qian, Fucui Tang, Dekun Tang, Yuanmou Li, Wenyi Wang, Mei Qin, Na Yin, Ping Zhan, Xiaodan Liu, Hongbo Chen
KEYWORDS:
Spinal Cord Injury, Microglial Activation, SIRT1, Smad3/TRIB3, Autophagy
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.3,
March
4,
2025
ABSTRACT: Background and Purpose: Spinal cord injury (SCI) manifests as a central nervous system disorder causing sensory and motor impairments. Preventing an overabundance of microglial activation is crucial in managing SCI. SIRT1 as a NAD-dependent deacetylase has the effect of ameliorating SCI, but its mechanism of action in microglia activation is still poorly understood. The objective of this research was to explore the role and process of SIRT1 in activating microglia during SCI. Methods: Laminectomy was conducted on the thoracic T10 region of rats, followed by striking the revealed spinal cord using an IH-0400 spinal cord impactor to create a model for SCI animals (n = 30). To create a model of BV2 inflammation, BV2 cells underwent a 24 h treatment with 1 μg/mL LPS. The expression of related proteins was detected by Western blot. Immunofluorescence staining, HE staining and Nissl staining were used to evaluate BV2 cell activation and spinal cord tissue injury in rats. Results: The research indicated minimal expression of SIRT1 in SCI cases, with its heightened expression ameliorating pathological damage and boosting neuron survival rates in SCI rats. Conversely, treatment with LPS markedly reduced autophagy in BV2 cells. Elevated levels of SIRT1 enhanced the production of autophagy-associated proteins LC3-II/I and Beclin1, reduced p62 expression, and curtailed the expression of the activation indicator IBA-1 in BV2 cells. Mechanistically, overexpression of SIRT1 inhibits the expression of TRIB3 by inhibiting Smad3 nuclear metastasis, thereby activating autophagy, inhibiting microglial overactivation and alleviating the development of SCI. Conclusion: Enhancing SIRT1 expression could reduce SCI progression by curbing the overactivation of microglia.