Department of Biology, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama-shi 223-8521, Japan.
Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Int J Mol Sci. 2022 Jan 27;23(3):1435. doi: 10.3390/ijms23031435.
The integrin family is involved in various biological functions, including cell proliferation, differentiation and migration, and also in the pathogenesis of disease. Integrins are multifunctional receptors that exist as heterodimers composed of α and β subunits and bind to various ligands, including extracellular matrix (ECM) proteins; they are found in many animals, not only vertebrates (e.g., mouse, rat, and teleost fish), but also invertebrates (e.g., planarian flatworm, fruit fly, nematodes, and cephalopods), which are used for research on genetics and social behaviors or as models for human diseases. In the present paper, we describe the results of a phylogenetic tree analysis of the integrin family among these species. We summarize integrin signaling in teleost fish, which serves as an excellent model for the study of regenerative systems and possesses the ability for replacing missing tissues, especially in the central nervous system, which has not been demonstrated in mammals. In addition, functions of astrocytes and reactive astrocytes, which contain neuroprotective subpopulations that act in concert with the ECM proteins tenascin C and osteopontin via integrin are also reviewed. Drug development research using integrin as a therapeutic target could result in breakthroughs for the treatment of neurodegenerative diseases and brain injury in mammals.
整合素家族参与各种生物学功能，包括细胞增殖、分化和迁移，也参与疾病的发病机制。整合素是多功能受体，存在由α和β亚基组成的异二聚体，并与各种配体结合，包括细胞外基质 (ECM) 蛋白；它们存在于许多动物中，不仅在脊椎动物（例如，小鼠、大鼠和硬骨鱼）中，而且在无脊椎动物（例如，扁形虫、果蝇、线虫和头足类动物）中，这些动物用于研究遗传学和社会行为或作为人类疾病的模型。在本文中，我们描述了这些物种中整合素家族的系统发育树分析结果。我们总结了硬骨鱼中的整合素信号转导，硬骨鱼是研究再生系统的理想模型，具有替换缺失组织的能力，尤其是在哺乳动物中尚未证明的中枢神经系统中。此外，还综述了星形胶质细胞和反应性星形胶质细胞的功能，这些细胞包含具有神经保护作用的亚群，它们通过整合素与 tenascin C 和骨桥蛋白等细胞外基质蛋白协同作用。将整合素作为治疗靶点的药物开发研究可能会为治疗哺乳动物的神经退行性疾病和脑损伤带来突破。
