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紧密连接蛋白在胶质肿瘤的发生与发展过程中的作用

Tight junction proteins in glial tumors development and progression.

作者信息

Moskal Jakub, Michalak Slawomir

机构信息

Department of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznan, Poland.

Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Poland.

出版信息

Front Cell Neurosci. 2025 Feb 3;19:1541885. doi: 10.3389/fncel.2025.1541885. eCollection 2025.

Abstract

Tight junctions form a paracellular barrier in epithelial and endothelial cells, and they regulate the diffusion of fluids, molecules, and the penetration of cells across tissue compartments. Tight junctions are composed of a group of integral membrane proteins, which include the claudin family, tight junction-associated Marvel protein family, junctional adhesion molecule family, and proteins that anchor the cytoskeleton, such as proteins and the cingulin family. Several factors, such as neurotransmitters or cytokines, and processes like ischemia/hypoxia, inflammation, tumorigenesis, phosphorylation/dephosphorylation, ubiquitination, and palmitoylation, regulate tight junction proteins. Claudins are involved in tumorigenesis processes that lead to glioma formation. In gliomas, there is a noticeable dysregulation of claudins, occludin, and abundance, and their dislocation has been observed. The weakening of intercellular adhesion and cell detachment is responsible for glioma infiltration into surrounding tissues. Furthermore, the paracellular permeability of the blood-brain barrier, formed with the involvement of tight junction proteins, influences the development of peritumoral edema - and, simultaneously, the rate of drug delivery to the glial tumor. Understanding the junctional and paracellular environments in brain tumors is crucial to predicting glial tumor progression and the feasibility of chemotherapeutic drug delivery. This knowledge may also illuminate differences between high and low-grade gliomas.

摘要

紧密连接在上皮细胞和内皮细胞中形成细胞旁屏障,并调节液体、分子的扩散以及细胞跨组织隔室的渗透。紧密连接由一组整合膜蛋白组成,包括claudin家族、紧密连接相关的MARVEL蛋白家族、连接黏附分子家族以及锚定细胞骨架的蛋白质,如 蛋白质和cingulin家族。神经递质或细胞因子等多种因素以及缺血/缺氧、炎症、肿瘤发生、磷酸化/去磷酸化、泛素化和棕榈酰化等过程调节紧密连接蛋白。Claudins参与导致胶质瘤形成的肿瘤发生过程。在胶质瘤中,claudins、occludin和 丰度存在明显失调,并且观察到它们的错位。细胞间黏附减弱和细胞脱离是胶质瘤浸润周围组织的原因。此外,由紧密连接蛋白参与形成的血脑屏障的细胞旁通透性影响瘤周水肿的发展,同时也影响药物向胶质肿瘤的递送速率。了解脑肿瘤中的连接和细胞旁环境对于预测胶质肿瘤进展和化疗药物递送的可行性至关重要。这些知识也可能阐明高级别和低级别胶质瘤之间的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9c/11830821/7039dd158466/fncel-19-1541885-g001.jpg

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