College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, 030619, PR China; Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, PR China.
Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, PR China.
Acta Histochem. 2019 Aug;121(6):742-749. doi: 10.1016/j.acthis.2019.07.001. Epub 2019 Jul 3.
Rheumatoid arthritis (RA) is a complicated chronic multisystem autoimmune disease, wherein the inflammatory cascade leads to vasospasm and osteoclastogenesis, which ultimately results in bone and cartilage destruction. In this study, we investigated the expression and localization of the alpha-7 nicotinic receptor (α7nAchR) gene CHRNA7 in the heart, liver, spleen, lung, kidney, and joints of the collagen-induced arthritis (CIA) rat model. The CHRNA7 mRNA and protein expression levels in these tissues of rats from CIA and normal groups were analyzed via real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The cellular localization of CHRNA7 protein was determined via immunohistochemistry (IHC) assays. CHRNA7 was expressed at varying levels in different tissues of rats from the groups, among which joints showed significantly higher CHRNA7 expression levels than other tissues (P < 0.05). CIA rats had significantly higher CHRNA7 expression levels in the spleen and joints than the control group rats (P < 0.05). Positive expression signals for CHRNA7 were detected in various tissues of CIA and control group rats, among which strong positive signals were detected in joint fibroblast-like synoviocytes (FLSs), endothelial cells, stromal cells, and macrophages. Our results further confirmed the involvement of the CAP in the onset and development of inflammatory responses in RA, suggesting that CHRNA7 may be a new therapeutic target for RA. This study is of great clinical and theoretical significance for understanding the differential expression of CHRNA7 in various tissues and cholinergic anti-inflammatory pathway (CAP)-targeted treatment of RA.
类风湿关节炎（RA）是一种复杂的慢性多系统自身免疫性疾病，其中炎症级联反应导致血管痉挛和破骨细胞生成，最终导致骨和软骨破坏。在这项研究中，我们研究了α-7 烟碱型乙酰胆碱受体（α7nAchR）基因 CHRNA7 在胶原诱导性关节炎（CIA）大鼠模型心脏、肝脏、脾脏、肺、肾脏和关节中的表达和定位。通过实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析 CIA 大鼠和正常大鼠各组织中 CHRNA7 mRNA 和蛋白的表达水平。通过免疫组织化学（IHC）检测 CHRNA7 蛋白的细胞定位。CHRNA7 在各组大鼠不同组织中的表达水平不同，其中关节的 CHRNA7 表达水平明显高于其他组织（P<0.05）。CIA 大鼠脾脏和关节中的 CHRNA7 表达水平明显高于对照组大鼠（P<0.05）。在 CIA 和对照组大鼠的各种组织中均检测到 CHRNA7 的阳性表达信号，其中在关节成纤维样滑膜细胞（FLSs）、内皮细胞、基质细胞和巨噬细胞中检测到强阳性信号。我们的结果进一步证实了 CAP 在 RA 炎症反应的发生和发展中的作用，提示 CHRNA7 可能是 RA 的一个新的治疗靶点。这项研究对于理解 CHRNA7 在不同组织中的差异表达以及针对胆碱能抗炎途径（CAP）的 RA 靶向治疗具有重要的临床和理论意义。
