A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
Fluids Barriers CNS. 2024 Nov 18;21(1):92. doi: 10.1186/s12987-024-00592-y.
Pericytes play a crucial role in controlling inflammation and vascular functions in the central nervous system, which are disrupted in Parkinson's disease (PD). Still, there is a lack of studies on the impact of pericytes on neurodegenerative diseases, and their involvement in the pathology of PD is unclear. Our objective was to investigate the molecular and functional differences between healthy pericytes and pericytes with the LRRK2 G2019S mutation, which is one of the most common mutations associated with PD.
Our study employed pericyte-like cells obtained from induced pluripotent stem cells produced from PD patients with the LRRK2 G2019S mutation as well as from healthy individuals. We examined the gene expression profiles of the cells and analyzed how the alterations reflect on their functionality.
We have shown differences in the expression of genes related to inflammation and angiogenesis. Furthermore, we observe modified migration speed in PD pericyte-like cells as well as enhanced secretion of inflammatory mediators, such as soluble VCAM-1 and MCP-1, in these pericyte-like cells following exposure to proinflammatory stimuli.
In summary, our findings support the notion that pericytes play a role in the inflammatory and vascular changes observed in PD. Further investigation of pericytes could provide valuable insight into understanding the pathogenesis of PD.
周细胞在中枢神经系统的炎症和血管功能控制中发挥着关键作用，而帕金森病（PD）会破坏这种作用。然而，目前关于周细胞对神经退行性疾病的影响的研究还很缺乏，其在 PD 病理中的作用也不清楚。我们的目的是研究健康周细胞和携带 LRRK2 G2019S 突变的周细胞之间的分子和功能差异，LRRK2 G2019S 突变是与 PD 关联最常见的突变之一。
我们的研究采用了诱导多能干细胞产生的周细胞样细胞，这些细胞来自于携带 LRRK2 G2019S 突变的 PD 患者和健康个体。我们检测了细胞的基因表达谱，并分析了这些变化如何反映在它们的功能上。
我们已经观察到与炎症和血管生成相关的基因表达存在差异。此外，我们还观察到 PD 周细胞样细胞的迁移速度发生改变，并且在受到促炎刺激后，这些周细胞样细胞会增强炎症介质的分泌，如可溶性 VCAM-1 和 MCP-1。
总之，我们的研究结果支持这样一种观点，即周细胞在 PD 中观察到的炎症和血管变化中发挥作用。进一步研究周细胞可以为理解 PD 的发病机制提供有价值的见解。
