Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.
Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.
Mol Med Rep. 2021 Nov;24(5). doi: 10.3892/mmr.2021.12385. Epub 2021 Aug 30.
Nephrolithiasis is the most common type of urinary system disease in developed countries, with high morbidity and recurrence rates. Nephrolithiasis is a serious health problem, which eventually leads to the loss of renal function and is closely related to hypertension. Modern medicine has adopted minimally invasive surgery for the management of kidney stones, but this does not resolve the root of the problem. Thus, nephrolithiasis remains a major public health issue, the causes of which remain largely unknown. Researchers have attempted to determine the causes and therapeutic targets of kidney stones and calculus‑related hypertension. Solute carrier family 26 member 6 (SLC26A6), a member of the well‑conserved solute carrier family 26, is highly expressed in the kidney and intestines, and it primarily mediates the transport of various anions, including OXa, HCO, Cl and SO, amongst others. Na‑dependent dicarboxylate‑1 (NADC‑1) is the Na‑carboxylate co‑transporter of the SLC13 gene family, which primarily mediates the co‑transport of Na and tricarboxylic acid cycle intermediates, such as citrate and succinate, amongst others. Studies have shown that Ca oxalate kidney stones are the most prevalent type of kidney stones. Hyperoxaluria and hypocitraturia notably increase the risk of forming Ca oxalate kidney stones, and the increase in succinate in the juxtaglomerular device can stimulate renin secretion and lead to hypertension. Whilst it is known that it is important to maintain the dynamic equilibrium of oxalate and citrate in the kidney, the synergistic molecular mechanisms underlying the transport of oxalate and citrate across kidney epithelial cells have undergone limited investigations. The present review examines the results from early reports studying oxalate transport and citrate transport in the kidney, describing the synergistic molecular mechanisms of SLC26A6 and NADC‑1 in the process of nephrolithiasis formation. A growing body of research has shown that nephrolithiasis is intricately associated with hypertension. Additionally, the recent investigations into the mediation of succinate via regulation of the synergistic molecular mechanism between the SLC26A6 and NADC‑1 transporters is summarized, revealing their functional role and their close association with the inositol triphosphate receptor‑binding protein to regulate blood pressure.
肾结石是发达国家最常见的泌尿系统疾病，发病率和复发率都很高。肾结石是一个严重的健康问题，最终会导致肾功能丧失，并且与高血压密切相关。现代医学已经采用微创外科手术来治疗肾结石，但这并没有解决根本问题。因此，肾结石仍然是一个主要的公共卫生问题，其病因在很大程度上尚不清楚。研究人员试图确定肾结石和结石相关高血压的病因和治疗靶点。溶质载体家族 26 成员 6（SLC26A6）是高度保守的溶质载体家族 26 的成员，在肾脏和肠道中高度表达，主要介导各种阴离子的转运，包括 OXa、HCO、Cl 和 SO 等。Na 依赖性二羧酸转运蛋白 1（NADC-1）是 SLC13 基因家族的 Na 羧酸盐共转运蛋白，主要介导 Na 和三羧酸循环中间产物（如柠檬酸和琥珀酸等）的共转运。研究表明，草酸钙肾结石是最常见的肾结石类型。高草酸尿症和低柠檬酸尿症显著增加形成草酸钙肾结石的风险，而近球装置中琥珀酸的增加可以刺激肾素分泌，导致高血压。虽然维持肾脏中草酸盐和柠檬酸的动态平衡很重要，但草酸钙和柠檬酸在肾上皮细胞中的转运的协同分子机制尚未得到充分研究。本综述回顾了早期关于肾脏中草酸盐转运和柠檬酸转运的研究结果，描述了 SLC26A6 和 NADC-1 在肾结石形成过程中的协同分子机制。越来越多的研究表明，肾结石与高血压密切相关。此外，还总结了最近关于琥珀酸通过调节 SLC26A6 和 NADC-1 转运蛋白协同分子机制来介导的研究结果，揭示了它们的功能作用及其与三磷酸肌醇受体结合蛋白的密切关联，以调节血压。
