研究动态
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一种通过间隙连接通道进行细胞间cAMP信号传递的二维有限元模型。

A two-dimensional finite element model of intercellular cAMP signaling through gap junction channels.

发表日期:2023 Apr 18
作者: P Dunn, N S Annamdevula, S J Leavesley, T C Rich, A-V Phan
来源: PHARMACOLOGY & THERAPEUTICS

摘要:

虽然环状腺苷酸单磷酸(cAMP)通常被视为细胞内信号,但已显示其可以通过连接素基的间隙连接通道在相邻细胞之间传播,促进间隙连接细胞间通讯(GJIC)。间隙连接介导的信号传递对许多组织的协调功能至关重要,并与心血管疾病、神经退行性疾病和癌症有关。特别是,它在肿瘤抑制或促进方面发挥着复杂的作用。本研究介绍了一个二维有限元模型,可以描述膜界面上具有间隙连接时的细胞间cAMP信号传递。该模型用于模拟通过肺微血管内皮细胞簇接口上的一个或两个间隙连接通道的cAMP传输。模拟结果发现,就GJIC而言,与文献观察基本一致。研究结果表明,如果可以实验测量其cAMP体积流速,则可以使用所提出的模型来评估间隙连接通道的渗透性能。版权所有 © 2023 Elsevier Ltd.。
While cyclic adenosine monophosphate (cAMP) is typically considered an intracellular signal, it has been shown to spread between adjacent cells through connexin-based gap junction channels, promoting gap junctional intercellular communication (GJIC). Gap junction-mediated signaling is critical for the coordinated function of many tissues, and have been linked with cardiovascular disease, neurogenerative disease, and cancers. In particular, it plays a complex role in tumor suppression or promotion. This work introduces a two-dimensional finite element model that can describe intercellular cAMP signaling in the presence of gap junctions on membrane interfaces. The model was utilized to simulate cAMP transfer through one and two gap junction channels on the interface of a cluster of two pulmonary microvascular endothelial cells. The simulation results were found to generally agree with what has been observed in the literature in terms of GJIC. The research outcomes suggest that the proposed model can be employed to evaluate the permeability properties of a gap junction channel if its cAMP volumetric flow rate can be experimentally measured.Copyright © 2023 Elsevier Ltd. All rights reserved.