Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components.

Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components.
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角叉菜胶诱导的大鼠后爪外周炎症和痛觉过敏的纵向转录图谱揭示了先天免疫系统成分的进行性招募。

DOI:
10.1016/j.jpain.2020.11.001
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发表时间:
2021-03
期刊:
影响因子:
4
通讯作者:
Iadarola, Michael J.
Iadarola, Michael J.
中科院分区:
医学2区
文献类型:
--
作者:
Goto, Taichi;Sapio, Matthew R.;Maric, Dragan;Robinson, Jeffrey M.;Saligan, Leorey N.;Mannes, Andrew J.;Iadarola, Michael J.

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疼痛是一种常见但可能使人衰弱的症状,通常需要复杂的管理策略。为了了解外周炎症和伤害性疼痛的分子动力学,我们研究了大鼠角叉菜胶诱导的外周炎症模型中行为、组织结构和转录组学特征的纵向变化。差异表达基因数量的顺序变化与关键白细胞群体(主要是中性粒细胞和巨噬细胞)的时间募集一致,每个波之前分别上调细胞特异性趋化因子Cxcl 1和Cxcl 2以及Ccl 2和Ccl 7。我们定义了12个基于表达模式的时间基因簇。在这些模式中,我们提取了包括炎性分泌组和其他与伤害性组织重塑和疼痛感觉相关的基因。注射后1小时即发生结构性组织变化,涉及多种胶原蛋白的上调,与炎症组织重塑一致。炎症表达谱揭示了一个广谱的,时间上协调的分子和细胞募集过程。这些结果为疼痛和炎症的调节提供了许多潜在的靶点。
Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour post-injection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation.
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