Sensory neuronal sensitisation occurs through HMGB-1-RAGE and TRPV1 in high-glucose conditions.
Sensory neuronal sensitisation occurs through HMGB-1-RAGE and TRPV1 in high-glucose conditions.
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DOI：
10.1242/jcs.215939
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发表时间：
2018-07-26
影响因子：
4
通讯作者：
Donaldson LF
中科院分区：
文献类型：
--
作者：
Bestall SM;Hulse RP;Blackley Z;Swift M;Ved N;Paton K;Beazley-Long N;Bates DO;Donaldson LF
已经提出了许多引起疼痛的糖尿病神经病变的潜在原因，包括细胞因子和生长因子的作用。高迁移率族蛋白 B1 (HMGB1) 是一种 RAGE（也称为 AGER）激动剂，其水平在糖尿病中升高，并通过调节外周炎症反应而导致疼痛。 HMGB1 通过未知机制增强幼稚动物的伤害感受行为。我们测试了 HMGB1 通过直接神经元激活 RAGE 和改变伤害性神经元反应性而引起疼痛的假设。当疼痛行为增强时，糖尿病大鼠的皮肤和初级感觉（背根神经节，DRG）神经元中的 HMGB1 和 RAGE 表达有时会增加。在培养的糖尿病大鼠 DRG 神经元和暴露于高葡萄糖浓度的幼稚大鼠的神经元中，激动剂诱发的 TRPV1 介导的 Ca2+ 反应增加。 HMGB1 介导的 DRG 神经元中 TRPV1 诱发的 Ca2+ 反应的增加是 RAGE 和 PKC 依赖性的，并且这可以通过共同施用生长因子剪接变体 VEGF-A165b 来阻断。 VEGF-A165b 治疗糖尿病大鼠体内疼痛行为和 DRG RAGE 表达增加被阻断。因此，我们得出结论，HMGB1–RAGE 激活在体外使 DRG 神经元敏感，而 VEGF-A165b 阻断 HMGB-1–RAGE DRG 激活，这可能有助于其体内镇痛特性。摘要：在高血糖条件下，伤害性神经元通过 HMGB1 通过 RAGE 和 PKC 的作用而变得敏感。这种致敏作用被 VEGF-A 剪接变体阻断。
Many potential causes for painful diabetic neuropathy have been proposed including actions of cytokines and growth factors. High mobility group protein B1 (HMGB1) is a RAGE (also known as AGER) agonist whose levels are increased in diabetes and that contributes to pain by modulating peripheral inflammatory responses. HMGB1 enhances nociceptive behaviour in naïve animals through an unknown mechanism. We tested the hypothesis that HMGB1 causes pain through direct neuronal activation of RAGE and alteration of nociceptive neuronal responsiveness. HMGB1 and RAGE expression were increased in skin and primary sensory (dorsal root ganglion, DRG) neurons of diabetic rats at times when pain behaviour was enhanced. Agonist-evoked TRPV1-mediated Ca2+ responses increased in cultured DRG neurons from diabetic rats and in neurons from naïve rats exposed to high glucose concentrations. HMGB1-mediated increases in TRPV1-evoked Ca2+ responses in DRG neurons were RAGE- and PKC-dependent, and this was blocked by co-administration of the growth factor splice variant VEGF-A165b. Pain behaviour and the DRG RAGE expression increases were blocked by VEGF-A165b treatment of diabetic rats in vivo. Hence, we conclude that HMGB1–RAGE activation sensitises DRG neurons in vitro, and that VEGF-A165b blocks HMGB-1–RAGE DRG activation, which may contribute to its analgesic properties in vivo. Summary: In high-glucose conditions, nociceptive neurons are sensitised through the actions of HMGB1 acting though RAGE and PKC. This sensitisation is blocked by a VEGF-A splice variant.
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DOI：
10.1016/j.bbi.2014.06.199
发表时间：
2014-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Allette YM;Due MR;Wilson SM;Feldman P;Ripsch MS;Khanna R;White FA
通讯作者：
White FA
影响因子：
9.3
作者：
Feldman P;Due MR;Ripsch MS;Khanna R;White FA
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White FA
影响因子：
4.2
作者：
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Zhong, Yi
DOI：
10.1124/jpet.106.116657
发表时间：
2007-06-01
影响因子：
3.5
作者：
Gunthorpe, Martin J.;Hannan, Sara Luis;Davis, John B.
通讯作者：
Davis, John B.
影响因子：
3.7
作者：
Cui, Yazhou;Zhou, Xiaoyan;Han, Jinxiang
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Han, Jinxiang