{"title":"镁在肾脏中的重吸收。","authors":"Jeroen H F de Baaij","doi":"10.1152/ajprenal.00298.2022","DOIUrl":null,"url":null,"abstract":"<p><p>Mg<sup>2+</sup> is essential for many cellular and physiological processes, including muscle contraction, neuronal activity, and metabolism. Consequently, the blood Mg<sup>2+</sup> concentration is tightly regulated by balanced intestinal Mg<sup>2+</sup> absorption, renal Mg<sup>2+</sup> excretion, and Mg<sup>2+</sup> storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg<sup>2+</sup> reabsorption in the kidney. In the proximal tubule, Mg<sup>2+</sup> reabsorption is dependent on paracellular permeability by claudin-2/12. In the thick ascending limb of Henle's loop, the claudin-16/19 complex provides a cation-selective pore for paracellular Mg<sup>2+</sup> reabsorption. The paracellular Mg<sup>2+</sup> reabsorption in this segment is regulated by the Ca<sup>2+</sup>-sensing receptor, parathyroid hormone, and mechanistic target of rapamycin (mTOR) signaling. In the distal convoluted tubule, the fine tuning of Mg<sup>2+</sup> reabsorption takes place by transcellular Mg<sup>2+</sup> reabsorption via transient receptor potential melastatin-like types 6 and 7 (TRPM6/TRPM7) divalent cation channels. Activity of TRPM6/TRPM7 is dependent on hormonal regulation, metabolic activity, and interacting proteins. Basolateral Mg<sup>2+</sup> extrusion is still poorly understood but is probably dependent on the Na<sup>+</sup> gradient. Cyclin M2 and SLC41A3 are the main candidates to act as Na<sup>+</sup>/Mg<sup>2+</sup> exchangers. Consequently, disturbances of basolateral Na<sup>+</sup>/K<sup>+</sup> transport indirectly result in impaired renal Mg<sup>2+</sup> reabsorption in the distal convoluted tubule. Altogether, this review aims to provide an overview of the molecular mechanisms of Mg<sup>2+</sup> reabsorption in the kidney, specifically focusing on transgenic mouse models and human hereditary diseases.</p>","PeriodicalId":7588,"journal":{"name":"American Journal of Physiology-renal Physiology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Magnesium reabsorption in the kidney.\",\"authors\":\"Jeroen H F de Baaij\",\"doi\":\"10.1152/ajprenal.00298.2022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mg<sup>2+</sup> is essential for many cellular and physiological processes, including muscle contraction, neuronal activity, and metabolism. Consequently, the blood Mg<sup>2+</sup> concentration is tightly regulated by balanced intestinal Mg<sup>2+</sup> absorption, renal Mg<sup>2+</sup> excretion, and Mg<sup>2+</sup> storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg<sup>2+</sup> reabsorption in the kidney. In the proximal tubule, Mg<sup>2+</sup> reabsorption is dependent on paracellular permeability by claudin-2/12. In the thick ascending limb of Henle's loop, the claudin-16/19 complex provides a cation-selective pore for paracellular Mg<sup>2+</sup> reabsorption. The paracellular Mg<sup>2+</sup> reabsorption in this segment is regulated by the Ca<sup>2+</sup>-sensing receptor, parathyroid hormone, and mechanistic target of rapamycin (mTOR) signaling. In the distal convoluted tubule, the fine tuning of Mg<sup>2+</sup> reabsorption takes place by transcellular Mg<sup>2+</sup> reabsorption via transient receptor potential melastatin-like types 6 and 7 (TRPM6/TRPM7) divalent cation channels. Activity of TRPM6/TRPM7 is dependent on hormonal regulation, metabolic activity, and interacting proteins. Basolateral Mg<sup>2+</sup> extrusion is still poorly understood but is probably dependent on the Na<sup>+</sup> gradient. Cyclin M2 and SLC41A3 are the main candidates to act as Na<sup>+</sup>/Mg<sup>2+</sup> exchangers. Consequently, disturbances of basolateral Na<sup>+</sup>/K<sup>+</sup> transport indirectly result in impaired renal Mg<sup>2+</sup> reabsorption in the distal convoluted tubule. Altogether, this review aims to provide an overview of the molecular mechanisms of Mg<sup>2+</sup> reabsorption in the kidney, specifically focusing on transgenic mouse models and human hereditary diseases.</p>\",\"PeriodicalId\":7588,\"journal\":{\"name\":\"American Journal of Physiology-renal Physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Physiology-renal Physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1152/ajprenal.00298.2022\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Physiology-renal Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajprenal.00298.2022","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Mg2+ is essential for many cellular and physiological processes, including muscle contraction, neuronal activity, and metabolism. Consequently, the blood Mg2+ concentration is tightly regulated by balanced intestinal Mg2+ absorption, renal Mg2+ excretion, and Mg2+ storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg2+ reabsorption in the kidney. In the proximal tubule, Mg2+ reabsorption is dependent on paracellular permeability by claudin-2/12. In the thick ascending limb of Henle's loop, the claudin-16/19 complex provides a cation-selective pore for paracellular Mg2+ reabsorption. The paracellular Mg2+ reabsorption in this segment is regulated by the Ca2+-sensing receptor, parathyroid hormone, and mechanistic target of rapamycin (mTOR) signaling. In the distal convoluted tubule, the fine tuning of Mg2+ reabsorption takes place by transcellular Mg2+ reabsorption via transient receptor potential melastatin-like types 6 and 7 (TRPM6/TRPM7) divalent cation channels. Activity of TRPM6/TRPM7 is dependent on hormonal regulation, metabolic activity, and interacting proteins. Basolateral Mg2+ extrusion is still poorly understood but is probably dependent on the Na+ gradient. Cyclin M2 and SLC41A3 are the main candidates to act as Na+/Mg2+ exchangers. Consequently, disturbances of basolateral Na+/K+ transport indirectly result in impaired renal Mg2+ reabsorption in the distal convoluted tubule. Altogether, this review aims to provide an overview of the molecular mechanisms of Mg2+ reabsorption in the kidney, specifically focusing on transgenic mouse models and human hereditary diseases.
期刊介绍:
The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.