Division of Nephrology, St Louis University, MO, USA.
Am J Kidney Dis. 2012 Mar;59(3):452-61. doi: 10.1053/j.ajkd.2011.10.054. Epub 2012 Jan 23.
Uromodulin, also known as Tamm-Horsfall protein, is a glycoprotein expressed exclusively by renal tubular cells lining the thick ascending limb of the loop of Henle. Although the physiologic functions of this protein remain elusive, significant progress has been made during the last decade that highlights the importance of uromodulin in the pathophysiology of various diseases, such as medullary cystic kidney disease, urinary tract infections, and nephrolithiasis. Meanwhile, there is renewed interest in the role of uromodulin in kidney injury, both acute and chronic. In this article, we review the existing evidence that supports a role for uromodulin in acute kidney injury, chronic kidney disease, and renal inflammation. Contrary to the conventional view of uromodulin as an instigator in kidney injury, new data from uromodulin knockout mice show a protective role for this protein in acute kidney injury, possibly through downregulating interstitial inflammation. In chronic kidney disease, uromodulin excretion, when adjusted for kidney function, is increased; the significance of this is unclear. Although it has been suggested that uromodulin exacerbates progressive kidney injury, we propose that the elevation in uromodulin secretion is instead reactive to injury and reflects an increase of uromodulin in the renal parenchyma, where it slows the injury process.
尿调蛋白，亦称 Tamm-Horsfall 蛋白，是一种糖蛋白，仅由肾近端小管细胞表达，这些细胞排列在亨利氏袢的升支粗段。尽管该蛋白的生理功能仍不清楚，但在过去十年中取得了重大进展，突显了尿调蛋白在各种疾病（如髓质囊性肾病、尿路感染和肾结石病）的病理生理学中的重要性。与此同时，人们对尿调蛋白在急性和慢性肾损伤中的作用重新产生了兴趣。本文综述了现有证据，这些证据支持尿调蛋白在急性肾损伤、慢性肾脏病和肾脏炎症中的作用。与尿调蛋白是肾损伤启动子的传统观点相反，来自尿调蛋白敲除小鼠的新数据表明，该蛋白在急性肾损伤中具有保护作用，可能是通过下调间质炎症。在慢性肾脏病中，尿调蛋白的排泄量（按肾功能调整）增加；其意义尚不清楚。尽管有人提出尿调蛋白加剧了进行性肾损伤，但我们提出，尿调蛋白分泌的增加是对损伤的反应，反映了尿调蛋白在肾实质中的增加，从而减缓了损伤过程。
