Effects of CFTR-ENaC on spinal cord edema after spinal cord injury.

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Open Medicine Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-1082
Guowei Shen, Yunpeng Zhang, Xinkun Cheng, Dongdong Li, Zhiyong Ding, Jiwei Tian, Hui Chen, Huiming Ding
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Abstract

Objective: To explore the role of cystic fibrosis transmembrane conduction regulator (CFTR)-Epithelial sodium channel (ENaC) in spinal cord edema after spinal cord injury (SCI) and the related mechanism.

Methods: Lipopolysaccharide (LPS)-treated M1830 astrocytes were applied as the SCI in vitro model. Immunohistochemistry, real-time PCR, and Western blotting were utilized to detect CFTR and ENaC expression. Enzyme-linked immunosorbent assay was used to measure inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-18. Transmission electron microscope examined ultrastructure changes, while CFTR-172 or Capsazepine treatment assessed their effects on edema and inflammation. Western blot analysis was employed to evaluate the PI3K, p-PI3K, AKT, and p-AKT signaling pathways in treated cells.

Results: LPS-treated M1830 cells exhibited increased levels of CFTR and pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, alongside decreased ENaC expression and suppressed p-PI3K/PI3K and p-AKT/AKT levels. Degeneration of the myelin sheath and axons was observed in LPS-treated M1830, while changes in ultrastructural were recovered after adding CFTR-172 or Capsazepine. The level of CFTR, TNF-α, IL-1β, IL-6, and IL-18 was decreased, while the level of ENaC, p-PI3K/PI3K, and p-AKT/AKT was increased obviously in LPS-treated M1830 with CFTR-172, Capsazepine, or IGF-1.

Conclusion: Down-regulation of CFTR and up-regulation of ENaC can attenuate inflammation in SCI by activating the PI3K/AKT signaling pathway, highlighting a new therapeutic approach for SCI treatment. These findings address a critical gap in current SCI treatments and suggest a novel intervention strategy targeting ion channel regulation.

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CFTR-ENaC 对脊髓损伤后脊髓水肿的影响
目的探讨囊性纤维化跨膜传导调节因子(CFTR)-上皮钠通道(ENaC)在脊髓损伤(SCI)后脊髓水肿中的作用及相关机制:方法:应用经脂多糖(LPS)处理的M1830星形胶质细胞作为SCI体外模型。免疫组化、实时 PCR 和 Western 印迹法检测 CFTR 和 ENaC 的表达。酶联免疫吸附试验用于检测炎症细胞因子,包括 TNF-α、IL-1β、IL-6 和 IL-18。透射电子显微镜检查了超微结构的变化,而 CFTR-172 或卡西平治疗则评估了它们对水肿和炎症的影响。采用 Western 印迹分析评估了处理细胞中的 PI3K、p-PI3K、AKT 和 p-AKT 信号通路:结果:经 LPS 处理的 M1830 细胞显示 CFTR 和促炎细胞因子(包括 TNF-α、IL-1β、IL-6 和 IL-18)水平升高,同时 ENaC 表达降低,p-PI3K/PI3K 和 p-AKT/AKT 水平受到抑制。在经 LPS 处理的 M1830 中观察到了髓鞘和轴突的退化,而在加入 CFTR-172 或卡西平后,超微结构的变化得到了恢复。CFTR、TNF-α、IL-1β、IL-6和IL-18的水平下降,而ENaC、p-PI3K/PI3K和p-AKT/AKT的水平在用CFTR-172、Capsazepine或IGF-1处理LPS的M1830中明显上升:结论:下调 CFTR 和上调 ENaC 可通过激活 PI3K/AKT 信号通路减轻 SCI 中的炎症反应,为 SCI 治疗提供了一种新的治疗方法。这些发现填补了目前 SCI 治疗方法的一个重要空白,并提出了一种针对离子通道调控的新型干预策略。
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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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