Dataset Information

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

ABSTRACT: 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. Here we report 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 cell division cycle 42 (CDC42) exhibited close associations with neuronal autophagy. Injection of 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. These findings suggest a potential interplay between GAL3 and CDC42 in regulating neuronal autophagy after SCI and indicate the therapeutic potential of targeting this pathway for enhancing recovery from spinal cord injuries.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE274319 | GEO | 2024/09/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets