Mutated LRRK2 induces a reactive phenotype and alters migration in human iPSC-derived pericyte-like cells.

IF 5.9 1区医学 Q1 NEUROSCIENCES Fluids and Barriers of the CNS Pub Date : 2024-11-18 DOI:10.1186/s12987-024-00592-y

Sanni Peltonen, Tuuli-Maria Sonninen, Jonna Niskanen, Jari Koistinaho, Marika Ruponen, Šárka Lehtonen

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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突变的 LRRK2 可诱导反应表型并改变人 iPSC 衍生的周细胞样细胞的迁移。

背景：周细胞在控制中枢神经系统的炎症和血管功能方面起着至关重要的作用，而帕金森病（PD）会破坏这些功能。然而，关于周细胞对神经退行性疾病的影响的研究仍然缺乏，而且它们参与帕金森病病理的情况也不清楚。我们的目的是研究健康周细胞与LRRK2 G2019S突变周细胞之间的分子和功能差异，LRRK2 G2019S突变是与帕金森病相关的最常见突变之一：我们的研究采用了从具有 LRRK2 G2019S 突变的帕金森病患者和健康人体内产生的诱导多能干细胞中获得的周细胞样细胞。我们研究了这些细胞的基因表达谱，并分析了这些改变对细胞功能的影响：结果：我们发现炎症和血管生成相关基因的表达存在差异。此外，我们还观察到帕金森病周细胞样细胞的迁移速度发生了改变，而且这些周细胞样细胞在受到促炎症刺激后分泌的炎症介质（如可溶性 VCAM-1 和 MCP-1）增多：总之，我们的研究结果支持这样一种观点，即在帕金森病中观察到的炎症和血管变化中，周细胞起到了一定的作用。对包膜细胞的进一步研究可为了解帕金森病的发病机制提供有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).