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Updated: Jun 21, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Galectin-3 alleviates demyelination by modulating microglial anti-inflammatory polarization through PPARγ-CD36 axis
Qian Wang1, Fansen Zeng2, Chunxiao Fang2
1Department of Infectious and Liver Diseases, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China; Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China.
Abstract:
Demyelination is characterized by disruption of myelin sheath and disorders in myelin formation. Currently, there are no effective therapeutic treatments available. Microglia, especially anti-inflammatory phenotype microglia are critical for remyelination. Galectin-3 (Gal-3), which is known to modulate microglia activation, is correlated with myelination. In this study, we aimed to elucidate the roles of Gal-3 during myelin formation and explore the efficiency and mechanism of rGal-3 administration in remyelination. We enrolled Gal-3 knockout (Lgals3 KO) mice and demonstrated Lgals3 KO causes demyelination during spontaneous myelinogenesis. We performed a cuprizone (CPZ) intoxication model and found Lgals3 KO aggravates demyelinated lesions and favors microglial pro-inflammatory phenotype polarization. Recombinant Gal-3 (rGal-3) administration alleviates CPZ intoxication and drives microglial towards anti-inflammatory phenotype. Additionally, RNA sequencing results reveal the correlation between Gal-3 and the PPARγ-CD36 axis. Thus, we performed SSO and GW9662 administration to inhibit the activation of the PPARγ-CD36 axis and found that rGal-3 administration modulates microglial phenotype polarization by regulating the PPARγ-CD36 axis. Together, our findings highlight the importance of Gal-3 in myelination and provide insights into rGal-3 administration for modulating microglial anti-inflammatory phenotype polarization through the PPARγ-CD36 axis.
Insights
Galectin-3 (Gal-3) is crucial for myelin repair. Administering recombinant Gal-3 (rGal-3) promotes myelin regeneration by shifting microglia to an anti-inflammatory state via the PPARγ-CD36 pathway.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Demyelination disrupts the myelin sheath, impacting neurological function, with limited therapeutic options.
- Microglia, particularly those with an anti-inflammatory phenotype, are essential for effective remyelination.
- Galectin-3 (Gal-3) influences microglial activation and is linked to myelination processes.
Purpose of the Study:
- To investigate the role of Gal-3 in myelin formation and remyelination.
- To evaluate the therapeutic potential and underlying mechanisms of recombinant Gal-3 (rGal-3) in promoting remyelination.
Main Methods:
- Utilized Gal-3 knockout (Lgals3 KO) mice to study demyelination during spontaneous myelinogenesis.
- Employed a cuprizone (CPZ)-induced demyelination model to assess the effects of Gal-3 deficiency and rGal-3 administration.
- Conducted RNA sequencing and pharmacological inhibition (SSO, GW9662) to explore the PPARγ-CD36 axis.
Main Results:
- Lgals3 KO mice exhibited demyelination and exacerbated lesions in the CPZ model, with a shift towards pro-inflammatory microglia.
- rGal-3 administration ameliorated CPZ-induced demyelination and promoted an anti-inflammatory microglial phenotype.
- Gal-3's effects on microglial polarization were mediated through the regulation of the PPARγ-CD36 signaling pathway.
Conclusions:
- Gal-3 plays a vital role in endogenous myelination and remyelination processes.
- rGal-3 administration represents a promising therapeutic strategy for demyelinating diseases by modulating microglial polarization.
- Targeting the Gal-3-mediated PPARγ-CD36 axis offers a novel approach for enhancing remyelination therapies.
