SLC26A6 and NADC‑1: Future direction of nephrolithiasis and calculus‑related hypertension research (Review).

Abstract

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 OXa2‑, HCO3‑, Cl‑ and SO42‑, 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 Ca2+ oxalate kidney stones are the most prevalent type of kidney stones. Hyperoxaluria and hypocitraturia notably increase the risk of forming Ca2+ 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.

• Authors: Xingyue Yang, Shun Yao, Jiaxing An, Hai Jin, Hui Wang, Biguang Tuo
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 24 Issue 5 (Nov 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 34458928 (Publication Type: Journal Article, Review)

Chemical References

• Citrates
• Dicarboxylic Acid Transporters
• Membrane Transport Proteins
• Organic Anion Transporters, Sodium-Dependent
• Oxalates
• SLC13A2 protein, human
• SLC26A6 protein, human
• Sulfate Transporters
• Symporters

Topics

• Citrates
• Dicarboxylic Acid Transporters (genetics, metabolism)
• Hyperoxaluria (metabolism)
• Hypertension (metabolism)
• Intestines
• Kidney (metabolism)
• Kidney Calculi (genetics, metabolism)
• Membrane Transport Proteins
• Nephrolithiasis (complications, genetics, metabolism)
• Organic Anion Transporters, Sodium-Dependent (genetics, metabolism)
• Oxalates (metabolism)
• Sulfate Transporters (genetics, metabolism)
• Symporters (genetics, metabolism)