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.
摘要：
脱髓鞘的特征在于髓鞘的破坏和髓鞘形成的紊乱。目前,没有有效的治疗方法。小胶质细胞,尤其是抗炎表型小胶质细胞是髓鞘再生的关键.半乳糖凝集素-3（Gal-3），已知可以调节小胶质细胞的激活，与髓鞘形成有关。在这项研究中,我们旨在阐明Gal-3在髓鞘形成过程中的作用,并探讨rGal-3在髓鞘再生过程中的应用效率和作用机制.我们招募了Gal-3敲除（Lgals3KO）小鼠，并证明了Lgals3KO在自发性髓鞘形成过程中会引起脱髓鞘。我们进行了铜宗（CPZ）中毒模型，发现Lgals3KO加重了脱髓鞘病变，并有利于小胶质细胞促炎表型极化。重组Gal-3(rGal-3)施用减轻CPZ中毒并驱动小胶质细胞朝向抗炎表型。此外,RNA测序结果揭示了Gal-3与PPARγ-CD36轴之间的相关性。因此，我们进行了SSO和GW9662给药,以抑制PPARγ-CD36轴的激活,并发现rGal-3给药通过调节PPARγ-CD36轴来调节小胶质细胞表型极化.一起,我们的研究结果强调了Gal-3在髓鞘形成中的重要性,并为rGal-3通过PPARγ-CD36轴调节小胶质细胞抗炎表型极化提供了见解.
