Lysophosphatidic acid activates satellite glia cells and Schwann cells
Lysophosphatidic acid activates satellite glia cells and Schwann cells
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DOI：
10.1002/glia.23585
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发表时间：
2019-05-01
期刊：
影响因子：
6.2
通讯作者：
Fischer，Michael J. M.
中科院分区：
文献类型：
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作者：
Robering，Jan W.;Gebhardt，Lisa;Fischer，Michael J. M.
瘙痒是肝胆疾病患者的常见且致残的症状，尤其是具有胆汁淤积特征的患者。患有肝脏瘙痒的患者血清中溶血磷脂酸（LPA）及其形成酶自分泌运动因子的水平升高，与瘙痒的严重程度和治疗反应相关。在这里，我们表明，在背根神经节培养物中，LPA 18:1 令人惊讶地激活了大部分卫星胶质细胞，并且对 LPA 18:1 的反应与对神经元表达的瞬时受体电位通道的反应呈反比相关。 LPA 18:1 仅引起异源表达的 TRPV1 的边缘激活，并且 TRPV1 缺陷小鼠的背根神经节培养物中的反应与对照组相似。 LPA 18:1 使随后对氯喹和 TGR5 激动剂 INT-777 的反应脱敏。 LPA 18:1 诱导的细胞质钙增加源于内质网。背根神经节和雪旺细胞中的 LPA 受体表达、LPAR1 免疫组织化学和药理学结果表明通过 LPA 受体 1 的信号传导途径。作为卫星胶质细胞的胶质细胞系的外周大鼠雪旺细胞也对 LPA 18:1 有反应。总而言之，LPA 18:1 主要激活神经胶质细胞而不是神经元，这可能随后调节神经元反应性和感觉，例如瘙痒和疼痛。
Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 18:1 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 18:1 correlated inversely with responses to neuronal expressed transient receptor potential channels. LPA 18:1 caused only a marginal activation of heterologously expressed TRPV1, and responses in dorsal root ganglion cultures from TRPV1‐deficient mice were similar to controls. LPA 18:1 desensitized subsequent responsiveness to chloroquine and TGR5 agonist INT‐777. The LPA 18:1‐induced increase in cytoplasmatic calcium stems from the endoplasmatic reticulum. LPA receptor expression in dorsal root ganglia and Schwann cells, LPAR1 immunohistochemistry, and pharmacological results indicate a signaling pathway through LPA receptor 1. Peripheral rat Schwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 18:1. Summarizing, LPA 18:1 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.