bFGF-2解除多发性硬化症纤粘连蛋白聚合体抑制髓鞘再生的研究

多发性硬化症病灶组织中，纤粘连蛋白聚合体抑制髓鞘再生可致轴突退化。纤粘连蛋白聚合体可调控小胶质细胞/巨噬细胞产生炎性因子抑制髓鞘再生。抑制纤粘连蛋白聚合体产生的炎性因子，或可成为促进多发性硬化症髓鞘再生的潜在治愈靶点。最近，我们研究发现bFGF-2可解除纤粘连蛋白聚合体对髓鞘再生的抑制作用；bFGF-2抑制纤粘连蛋白聚合体诱导小胶质细胞/巨噬细胞产生炎性因子；bFGF-2调控纤粘连蛋白聚合体诱导小胶质细胞系（BV2）炎性因子产生的信号通路。这表明，bFGF-2可能抑制纤粘连蛋白聚合体诱导小胶质细胞/巨噬细胞产生炎性因子，解除纤粘连蛋白聚合体对髓鞘再生的抑制。因此，本项目通过原代细胞培养、脑组织培养、脱髓鞘的小鼠模型和多发性硬化症病灶组织，研究bFGF-2解除纤粘连蛋白聚合体抑制髓鞘再生的机制。本项目的研究将为治疗多发性硬化症研究带来新理论和认识。

Failure of remyelination in the chronic demyelinating disease multiple sclerosis (MS) results in secondary axon degeneration and therefore contributes to disease progression. Fibronectin aggregates (aFn) are major constituents of the extracellular matrix in the MS lesion microenvironment that perturb remyelination by preventing oligodendrocyte progenitor cell (OPC) maturation and by interfering with proper activation of resident microglia and infiltrating macrophages. Hence, the inhibitory signals induced by aFn, factors that clear aFn or factors that affect aFn per se could be potential therapeutic targets for promoting remyelination. Recently, our results show that bFGF-2 overcomes aFn-mediated inhibition of remyelination upon forebrain organotypic slice culture. Although bFGF-2 hardly promotes OPCs differentiation, bFGF-2 modulates microglia/macrophages to rescue remyelination from aFn inhibition by reducing proinflammatory cytokines. Also, we find that bFGF-2 regulates the signaling pathway of proinflammatory cytokines production and ECM interactions upon aFn activated microglia cell lines. This research is aiming for mechanism that bFGF-2 rescues remyelination from aFn-impairing. The research outcomes expand the knowledge for preventing the inhibitory signals induced by aFn and designing pharmacological strategies to manipulate the molecular microenvironment in the damaged nervous system to promote myelin repair in MS.