Galactin-3 regulation of CDC42 promotes neuronal autophagy following spinal cord injury

Lei Yan¹Xun Zhou¹Qianqiu Li¹Hongxiang Hong¹Chunshuai Wu¹Yong-Jing Gao^2,3*Guanhua Xu^1*Zhiming Cui^1*

• ¹Second Affiliated Hospital of Nantong University, Nantong, China
• ²Institute of Pain Medicine and Special Environmental Medicine of Nantong University, Nantong, China
• ³Nantong University, Nantong, China

Background: Spinal cord injury (SCI) is a debilitating condition within the nervous system with a high disability rate and substantial economic burden. The functional recovery following SCI is enhanced by moderate levels of autophagy but hindered when autophagy becomes excessive. Galectin-3 (GAL3) has been recognized as an autophagy regulator; however, its role in SCI and its associated mechanism are largely unknown. Results: We found that GAL3 was increased in spinal neurons and serum in SCI rats, and knockdown or inhibition of GAL3 promoted motor function recovery. The bioinformatics analysis showed that GAL3 is closely related to programmed cell death after SCI. Indeed, the knockdown of GAL3 resulted in a decrease in autophagy markers ATG7 and LC3 II/I ratio, along with an increase in P62 expression. Furthermore, GAL3 and CDC42 exhibited close associations with neuronal autophagy. Injection of siR-CDC42 and CDC42 inhibitor ML141 effectively reduced GAL3-mediated enhancement of neuronal autophagy. Additionally, CDC42 was increased in spinal neurons post-SCI, and administration of ML141 decreased the expression of autophagy markers and improved motor function recovery. Importantly, elevated levels of GAL3 and CDC42 were observed in the serum of SCI patients.