Regulation of renal aquaporins: implications in tubular epithelial integrity

Aquaporins (AQPs) are crucial membrane proteins that primarily facilitate water transport across cell membranes. In the kidneys, AQP1, AQP7, AQP8, and AQP11 are expressed in the proximal tubules. AQP1 is also localized to the thin descending limb of the loop of Henle. AQP2, AQP3, AQP4, AQP5, and AQP6 are expressed in the collecting ducts. Specific AQPs, such as aquaglyceroporins and peroxiporins, also transport solutes like glycerol and hydrogen peroxide, indicating their broader physiological roles beyond water permeability. Renal AQPs play a fundamental role in urine concentration and maintaining water balance. However, some studies using AQP knockout mouse models have reported structural abnormalities in the renal tubules, along with defective water handling. These findings highlight the involvement of AQPs in regulating cell proliferation, migration, and apoptosis, which are essential processes for maintaining tubular integrity. Furthermore, aquaglyceroporins and peroxiporins are implicated in modulating cellular redox balance and contributing to oxidative stress responses that are also associated with tubular damage. This review explores how AQPs are regulated under physiological conditions and how they become dysregulated in kidney diseases such as acute kidney injury, diabetic kidney disease, and polycystic kidney disease. Understanding these mechanisms may help in identifying new therapeutic strategies targeting AQPs in renal pathologies.