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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1554945
Tauroursodeoxycholic acid regulates macrophage/monocyte distribution and improves spinal microenvironment to promote nerve regeneration through inhibiting NF-κB signaling pathway in spinal cord injury
Provisionally accepted
Yonghui Hou 1
Yage Zhang 2 Dan Luo 1 Wanshun Wang 2 Shunmei E 1 Chengxi Huang 3 Yu Hou 1
Shudong Chen 1
Jiheng Zhan 1
Liangliang Xu 2*
Dingkun Lin 1*- 1 Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
- 2 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- 3 The Culver Academies, Culver, United States
Following spinal cord injury (SCI), blood-borne monocytes infiltrate the spinal cord, differentiate into macrophages, and dominate the lesion site. Inflammatory responses mediated by macrophages determine nerve regeneration and functional recovery after SCI. Tauroursodeoxycholic acid (TUDCA) shows a neuroprotective effect in different SCI animal models. However, the underlying mechanism of TUDCA regulating monocytes/macrophages to impact nerve regeneration after SCI has not been elucidatedclearly. This study aims to investigate the effect of TUDCA on monocyte/macrophage distribution and nerve regeneration in the subacute stage of SCI. Transwell analysis, Bromodeoxyuridine (BrdU) staining, and TUNEL staining were performed to evaluate the effect of TUDCA on regulating the inflammatory response to impact spinal neural stem cells (NSCs) proliferation and migration, spinal neuron survival, and axon degeneration in vitro. H&E staining, RNA sequencing, and a series of immunofluorescent staining were performed to investigate the pathological progress, gene expression changes, monocytes/macrophages distribution, and nerve regeneration after TUDCA treatment in SCI mice. We found TUDCA restored spinal NSCs migration and proliferation and reduced spinal NSCs and neurons apoptosis and axon degeneration by regulating inflammatory response in vitro. TUDCA treatment promoted wound healing, down-regulated genes related to inflammatory response, and up-regulated genes related to spinal cord development in SCI mice. Our study provided evidence that TUDCA treatment regulated monocyte/macrophage distribution and improved the microenvironment to promote nerve regeneration in SCI mice.
Keywords: tauroursodeoxycholic acid, spinal cord injury, monocyte, macrophage, microenvironment, Nerve Regeneration, Inflammation
Received: 03 Jan 2025; Accepted: 24 Mar 2025.
Copyright: © 2025 Hou, Zhang, Luo, Wang, E, Huang, Hou, Chen, Zhan, Xu and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liangliang Xu, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China
Dingkun Lin, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
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