Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan.
Komatsu University, Komatsu 923-0921, Japan.
Int J Mol Sci. 2022 Feb 14;23(4):2086. doi: 10.3390/ijms23042086.
Non-enzymatic glycation is an unavoidable reaction that occurs across biological taxa. The final products of this irreversible reaction are called advanced glycation end-products (AGEs). The endogenously formed AGEs are known to be bioactive and detrimental to human health. Additionally, exogenous food-derived AGEs are debated to contribute to the development of aging and various diseases. Receptor for AGEs (RAGE) is widely known to elicit biological reactions. The binding of RAGE to other ligands (e.g., high mobility group box 1, S100 proteins, lipopolysaccharides, and amyloid-β) can result in pathological processes via the activation of intracellular RAGE signaling pathways, including inflammation, diabetes, aging, cancer growth, and metastasis. RAGE is now recognized as a pattern-recognition receptor. All mammals have RAGE homologs; however, other vertebrates, such as birds, amphibians, fish, and reptiles, do not have RAGE at the genomic level. This evidence from an evolutionary perspective allows us to understand why mammals require RAGE. In this review, we provide an overview of the scientific knowledge about the role of RAGE in physiological and pathological processes. In particular, we focus on (1) RAGE biology, (2) the role of RAGE in physiological and pathophysiological processes, (3) RAGE isoforms, including full-length membrane-bound RAGE (mRAGE), and the soluble forms of RAGE (sRAGE), which comprise endogenous secretory RAGE (esRAGE) and an ectodomain-shed form of RAGE, and (4) oxytocin transporters in the brain and intestine, which are important for maternal bonding and social behaviors.
非酶糖基化是一种不可避免的反应，发生在生物分类群中。这个不可逆反应的最终产物被称为晚期糖基化终末产物（AGEs）。内源性形成的 AGEs 已知具有生物活性，对人类健康有害。此外，外源性食物来源的 AGEs 被认为有助于衰老和各种疾病的发展。AGEs 的受体（RAGE）被广泛认为会引起生物学反应。RAGE 与其他配体（例如高迁移率族框 1、S100 蛋白、脂多糖和淀粉样β）的结合会通过激活细胞内 RAGE 信号通路，包括炎症、糖尿病、衰老、癌症生长和转移，导致病理过程。RAGE 现在被认为是一种模式识别受体。所有哺乳动物都有 RAGE 同源物；然而，其他脊椎动物，如鸟类、两栖动物、鱼类和爬行动物，在基因组水平上没有 RAGE。从进化的角度来看，这一证据使我们能够理解为什么哺乳动物需要 RAGE。在这篇综述中，我们提供了关于 RAGE 在生理和病理过程中的作用的科学知识概述。特别是，我们重点介绍了（1）RAGE 生物学，（2）RAGE 在生理和病理生理过程中的作用，（3）RAGE 同工型，包括全长膜结合 RAGE（mRAGE）和 RAGE 的可溶性形式（sRAGE），其包括内源性分泌 RAGE（esRAGE）和 RAGE 的一个胞外结构域脱落形式，以及（4）脑和肠中的催产素转运体，它们对母婴结合和社会行为很重要。
