背景:肿瘤周围脑水肿(PTBE)已被广泛报道为许多脑肿瘤,尤其是神经胶质瘤.由于血脑屏障(BBB)对于保持最小的渗透性至关重要,BBB成分相互作用的任何改变,特别是在星形胶质细胞和紧密连接(TJ)中,会破坏血脑屏障的稳态并使其严重渗漏,随后产生水肿。
目的:本研究旨在通过检查claudin(CLDN)基因表达和瞬时受体电位(TRP)膜通道表达的变化来评估BBB的功能神经胶质血管单元,另外定义它们的表达式之间的相关性。使用体外球体肿胀模型和来自患有PTBE的神经胶质瘤患者的肿瘤样品进行评估。
结果:球体模型的结果显示,基因TRPC3,TRPC4,TRPC5和TRPV1在胶质瘤细胞中上调,无论是野生型异柠檬酸脱氢酶1(IDH1)还是IDH1R132H突变体,有或没有NaCl处理。此外,TRP基因似乎与CLDN1、CLDN3和CLDN5基因的上调有不利的相关性。此外,IDH1mt-R132H胶质瘤细胞中TRPC1和TRPC4的上调。另一方面,相关性分析显示PTBE中不同蛋白之间的相关性不同。CLDN1与CLDN3表现出轻微的正相关。同样,TRPV1与TRPC1呈轻微正相关。相比之下,TRPC4与TRPC5呈轻微负相关。另一方面,TRPC3显示出与TRPC5的轻微正相关,而非PTBE分析突出显示CLDN1和TRPM4之间的中度正相关,而CLDN3显示出与TRPC4的中度负相关。此外,CLDN5与TRPC4呈轻微负相关,但与TRPC3呈中等正相关。此外,TRPC1与TRPV1呈轻微负相关,TRPC3与TRPC4呈轻微正相关,TRPV1与TRPC5呈轻微负相关。
结论:作为结论,本研究提供了PTBE患者中TRPs和CLDN基因表达之间存在轻微负相关的证据,以及水肿细胞模型中某些基因的确证结果.
BACKGROUND: Peritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema.
OBJECTIVE: This study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions. The evaluation was conducted using in vitro spheroid swelling models and tumor samples from glioma patients with PTBE.
RESULTS: The results of the spheroid model showed that the genes TRPC3, TRPC4, TRPC5, and TRPV1 were upregulated in glioma cells either wild-type isocitrate dehydrogenase 1 (IDH1) or the IDH1 R132H mutant, with or without NaCl treatment. Furthermore, TRP genes appeared to adversely correlate with the up regulation of CLDN1, CLDN3, and CLDN5 genes. Besides, the upregulation of TRPC1 and TRPC4 in IDH1mt-R132H glioma cells. On the other hand, the correlation analysis revealed different correlations between different proteins in PTBE. CLDN1 exhibits a slight positive correlation with CLDN3. Similarly, TRPV1 displays a slight positive correlation with TRPC1. In contrast, TRPC4 shows a slight negative correlation with TRPC5. On the other hand, TRPC3 demonstrates a slight positive correlation with TRPC5, while the non-PTBE analysis highlights a moderate positive correlation between CLDN1 and TRPM4 while CLDN3 exhibits a moderate negative correlation with TRPC4. Additionally, CLDN5 demonstrates a slight negative correlation with TRPC4 but a moderate positive correlation with TRPC3. Furthermore, TRPC1 have a slight negative correlation with TRPV1, TRPC3 exhibiting a slight positive correlation with TRPC4, and TRPV1 showing a slight negative correlation with TRPC5.
CONCLUSIONS: As a conclusion, the current study provided evidence of a slight negative correlation between TRPs and CLDN gene expression in PTBE patients and confirmatory results with some of the genes in cell model of edema.