Tight junction and kidney stone disease

ABSTRACT

Defects of tight junction (TJ) are involved in many diseases related to epithelial cell functions, including kidney stone disease (KSD), which is a common disease affecting humans for over a thousand years. This review provides brief overviews of KSD and TJ, and summarizes the knowledge on crystal-induced defects of TJ in renal tubular epithelial cells (RTECs) in KSD. Calcium oxalate (CaOx) crystals, particularly COM, disrupt TJ via p38 MAPK and ROS/Akt/p38 MAPK signaling pathways, filamentous actin (F-actin) reorganization and α-tubulin relocalization. Stabilizing p38 MAPK signaling, reactive oxygen species (ROS) production, F-actin and α-tubulin by using SB239063, N-acetyl-L-cysteine (NAC), phalloidin and docetaxel, respectively, successfully prevent the COM-induced TJ disruption and malfunction. Additionally, genetic disorders of renal TJ, including mutations and single nucleotide polymorphisms (SNPs) of CLDN2, CLDN10b, CLDN14, CLDN16 and CLDN19, also affect KSD. Finally, the role of TJ as a potential target for KSD therapeutics and prevention is also discussed.

KEYWORDS:

• Calcium oxalate
• claudins
• docetaxel
• occludin
• phalloidin
• ROS
• SB239063
• TER
• ZO-1

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data sharing does not apply to this review article as no new data were generated.

Additional information

Funding

The work was supported by the National Research Council of Thailand (NRCT): High-Potential Research Team Grant Program (grant no. N42A660625).