人椎间盘组织肾素-血管紧张素系统。

IF 3.2 3区 医学 Q3 CELL & TISSUE ENGINEERING
Z Li, L Wystrach, A Bernstein, S Grad, M Alini, R G Richards, D Kubosch, N Südkamp, K Izadpanah, E J Kubosch, G Lang
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引用次数: 11

摘要

症状性椎间盘(IVD)退变是严重的社会经济负担。最近,研究人员证实了组织肾素-血管紧张素系统(tRAS)在大鼠和牛IVD中的表达。tRAS的主要效应物是血管紧张素II (AngII),它参与促炎途径。本研究探讨了tRAS在人IVD中的表达,以及tRAS与炎症和IVD变性的关系。在脊柱手术中收集人体IVD组织,并根据主要诊断进行分布。评估IVD组织中tRAS组分、促炎和分解代谢标志物的基因表达。测定IVD组织中羟脯氨酸(OHP)和糖胺聚糖(GAG)的含量。免疫组化法观察tRAS组分的组织分布。血管紧张素转换酶(ACE)、Ang II受体2型(AGTR2)、血管紧张素原(AGT)和组织蛋白酶D (CTSD)等tRAS成分在人ivd中均有表达。与tRAS阴性样本(n = 37)相比,表达tRAS成分的IVD样本(n = 21)显示白细胞介素6 (IL-6)、肿瘤坏死因子α (TNF-α)、带血栓反应蛋白基元的崩解素和金属蛋白酶(ADAMTS) 4和5的表达水平显著高于tRAS阴性样本(n = 37)。在tras阳性样本中,AGT、基质金属蛋白酶13和3、IL-1、IL-6和IL-8在创伤性ivd中的表达高于退化性ivd。与tRAS阳性组织相比,未表达tRAS的IVD组织的总GAG/DNA含量显著升高。免疫组织化学证实了AngII在人IVD中的存在。本研究确定了tRAS在人类IVD中的存在,并提示tRAS表达与炎症和最终IVD变性之间存在相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The tissue-renin-angiotensin-system of the human intervertebral disc.

Symptomatic intervertebral disc (IVD) degeneration accounts for significant socioeconomic burden. Recently, the expression of the tissue renin-angiotensin system (tRAS) in rat and bovine IVD was demonstrated. The major effector of tRAS is angiotensin II (AngII), which participates in proinflammatory pathways. The present study investigated the expression of tRAS in human IVDs, and the correlation between tRAS, inflammation and IVD degeneration. Human IVD tissue was collected during spine surgery and distributed according to principal diagnosis. Gene expression of tRAS components, proinflammatory and catabolic markers in the IVD tissue was assessed. Hydroxyproline (OHP) and glycosaminoglycan (GAG) content in the IVD tissue were determined. Tissue distribution of tRAS components was investigated by immunohistochemistry. Gene expression of tRAS components such as angiotensin-converting enzyme (ACE), Ang II receptor type 2 (AGTR2), angiotensinogen (AGT) and cathepsin D (CTSD) was confirmed in human IVDs. IVD samples that expressed tRAS components (n = 21) revealed significantly higher expression levels of interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5 compared to tRAS-negative samples (n = 37). Within tRAS-positive samples, AGT, matrix-metalloproteinases 13 and 3, IL-1, IL-6 and IL-8 were more highly expressed in traumatic compared to degenerated IVDs. Total GAG/DNA content of non-tRAS expressing IVD tissue was significantly higher compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD. The present study identified the existence of tRAS in the human IVD and suggested a correlation between tRAS expression, inflammation and ultimately IVD degeneration.

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来源期刊
European cells & materials
European cells & materials 生物-材料科学:生物材料
CiteScore
6.00
自引率
6.50%
发文量
55
审稿时长
1.5 months
期刊介绍: eCM provides an interdisciplinary forum for publication of preclinical research in the musculoskeletal field (Trauma, Maxillofacial (including dental), Spine and Orthopaedics). The clinical relevance of the work must be briefly mentioned within the abstract, and in more detail in the paper. Poor abstracts which do not concisely cover the paper contents will not be sent for review. Incremental steps in research will not be entertained by eCM journal.Cross-disciplinary papers that go across our scope areas are welcomed.
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