University of Torino School of Medicine, Torino, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy.
Cytokine Growth Factor Rev. 2021 Feb;57:55-63. doi: 10.1016/j.cytogfr.2020.05.006. Epub 2020 Sep 2.
Cell-cell communication is pivotal to guide embryo development, as well as to maintain adult tissues homeostasis and control immune response. Among extracellular factors responsible for this function, are the Semaphorins, a broad family of around 20 different molecular cues conserved in evolution and widely expressed in all tissues. The signaling cascades initiated by semaphorins depend on a family of conserved receptors, called Plexins, and on several additional molecules found in the receptor complexes. Moreover, multiple intracellular pathways have been described to act downstream of semaphorins, highlighting significant diversity in the signaling cascades controlled by this family. Notably, semaphorin expression is altered in many human diseases, such as immunopathologies, neurodegenerative diseases and cancer. This underscores the importance of semaphorins as regulatory factors in the tissue microenvironment and has prompted growing interest for assessing their potential relevance in medicine. This review article surveys the main contexts in which semaphorins have been found to regulate developing and healthy adult tissues, and the signaling cascades implicated in these functions. Vis a vis, we will highlight the main pathological processes in which semaphorins are thought to have a role thereof.
细胞间通讯对于指导胚胎发育以及维持成人组织的内稳态和控制免疫反应至关重要。在负责此功能的细胞外因子中，有一类广泛存在于进化过程中的信号蛋白家族，称为 Semaphorins，它们在所有组织中广泛表达。Semaphorins 引发的信号级联反应依赖于一组保守的受体，称为 Plexins，以及受体复合物中发现的几种其他分子。此外，已经描述了多种细胞内途径来发挥信号级联反应的下游作用，这突出了由该家族控制的信号级联反应的显著多样性。值得注意的是，Semaphorin 的表达在许多人类疾病中发生改变，例如免疫病理学、神经退行性疾病和癌症。这突显了 Semaphorin 作为组织微环境中调节因子的重要性，并促使人们越来越关注评估它们在医学中的潜在相关性。这篇综述文章调查了 Semaphorin 被发现调节发育中和健康成人组织的主要背景，以及涉及这些功能的信号级联反应。因此，我们将强调 Semaphorin 被认为在其中发挥作用的主要病理过程。
