Jia Qingxia, Huang Ziye, Wang Guang, Sun Xia, Wu Yuyun, Yang Bowei, Yang Tongxin, Liu Jianhe, Li Pei, Li Jiongming
The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2022 Nov 9;13:1036423. doi: 10.3389/fphar.2022.1036423. eCollection 2022.
The incidence of kidney stones averages 10%, and the recurrence rate of kidney stones is approximately 10% at 1 year, 35% at 5 years, 50% at 10 years, and 75% at 20 years. However, there is currently a lack of good medicines for the prevention and treatment of kidney stones. Osteopontin (OPN) is an important protein in kidney stone formation, but its role is controversial, with some studies suggesting that it inhibits stone formation, while other studies suggest that it can promote stone formation. OPN is a highly phosphorylated protein, and with the deepening of research, there is growing evidence that it promotes stone formation, and the phosphorylated protein is believed to have adhesion effect, promote stone aggregation and nucleation. In addition, OPN is closely related to immune cell infiltration, such as OPN as a pro-inflammatory factor, which can activate mast cells (degranulate to release various inflammatory factors), macrophages (differentiated into M1 macrophages), and T cells (differentiated into T1 cells) etc., and these inflammatory cells play a role in kidney damage and stone formation. In short, OPN mainly exists in the phosphorylated form in kidney stones, plays an important role in the formation of stones, and may be an important target for drug therapy of kidney stones.
肾结石的发病率平均为10%，其复发率在1年时约为10%，5年时为35%，10年时为50%，20年时为75%。然而，目前缺乏防治肾结石的有效药物。骨桥蛋白（OPN）是肾结石形成过程中的一种重要蛋白质，但其作用存在争议，一些研究表明它能抑制结石形成，而另一些研究则表明它可促进结石形成。OPN是一种高度磷酸化的蛋白质，随着研究的深入，越来越多的证据表明它促进结石形成，且磷酸化蛋白被认为具有黏附作用，可促进结石聚集和成核。此外，OPN与免疫细胞浸润密切相关，例如OPN作为一种促炎因子，可激活肥大细胞（脱颗粒释放各种炎症因子）、巨噬细胞（分化为M1巨噬细胞）和T细胞（分化为T1细胞）等，而这些炎症细胞在肾脏损伤和结石形成中发挥作用。简而言之，OPN在肾结石中主要以磷酸化形式存在，在结石形成中起重要作用，可能是肾结石药物治疗的重要靶点。
