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解析水通道蛋白在代谢性疾病中的作用:一篇小综述。

Deciphering the role of aquaporins in metabolic diseases: A mini review.

机构信息

Animal Physiology and Biochemistry Laboratory, Department of Zoology, Gauhati University, Jalukbari, Guwahati, India.

Animal Physiology and Biochemistry Laboratory, Department of Zoology, Gauhati University, Jalukbari, Guwahati, India.

出版信息

Am J Med Sci. 2022 Aug;364(2):148-162. doi: 10.1016/j.amjms.2021.10.029. Epub 2022 Feb 20.

Abstract

The expression of various isoforms of aquaporins (AQPs) in different tissues and organs of the body makes it a viable candidate for being responsible for maintaining cell stability and integrity as their involvement has been well documented in a number of pathophysiological conditions of the human body. Any alteration in the cellular environment brought about by these AQPs creates severe downstream effects like changes in cellular osmolality, volume, ionic composition, signaling pathways and even in the levels of intracellular second messengers and, as such, facilitates the occurrence of diseases like cancer. The altered equilibrium of water, extracellular ions and amino acid neurotransmitters caused by neuronal destruction and oxidative stress in neurodegenerative diseases proposed the role of these AQPs in these diseased conditions as well. The association of AQPs in a variety of inflammatory processes like lung injury, brain edema, neuromyelitis optica, and colitis as manifested through their dysregulation both in animal and human diseases is truly an eye opener for their role in protection and reaction to various noxious stimuli including bacterial infection. Renal diseases like nephrogenic diabetes inspidus, autosomal dominant polycystic kidney disease and acute kidney injury are some of the pathophysiological conditions related to malfunctioning of aquaporins. Besides, the malfunctioning of aquaglyceroporins like AQP7 and AQP9 makes them responsible for disorders like obesity, nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. In this review article, we present our current understanding of the role of AQPs in the causation of these metabolic disorders and how targeting them holds promising therapeutic potential for most of these diseases like cancer, renal diseases and even cardiovascular disorders.

摘要

水通道蛋白(AQP)的各种同工型在体内不同组织和器官中的表达,使它成为维持细胞稳定性和完整性的候选蛋白,因为其在人体许多病理生理条件下的作用已得到充分证实。这些 AQP 引起的细胞环境变化会产生严重的下游效应,如细胞渗透压、体积、离子组成、信号通路甚至细胞内第二信使水平的变化,从而促进癌症等疾病的发生。在神经退行性疾病中,神经元破坏和氧化应激引起的水、细胞外离子和氨基酸神经递质平衡的改变,也提出了这些 AQP 在这些疾病状态中的作用。AQP 在各种炎症过程中的关联,如肺损伤、脑水肿、视神经脊髓炎和结肠炎,以及在动物和人类疾病中它们的失调都表明了它们在保护和对各种有害刺激(包括细菌感染)的反应中的作用。肾源性糖尿病、常染色体显性多囊肾病和急性肾损伤等肾脏疾病是与水通道蛋白功能障碍相关的病理生理条件之一。此外,AQP7 和 AQP9 等水甘油通道蛋白的功能障碍使它们成为肥胖、非酒精性脂肪性肝病和非酒精性脂肪性肝炎等疾病的罪魁祸首。在这篇综述文章中,我们介绍了目前对 AQP 在这些代谢紊乱引起中的作用的理解,以及针对这些蛋白的治疗方法对癌症、肾脏疾病甚至心血管疾病等大多数疾病具有潜在的治疗价值。

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