The excretory system starts at the kidneys, a pair of organs that detoxify and remove waste from the blood. This waste, in the form of urine, is transported through the ureters to the bladder, where urine is stored until it is excreted through the urethra. Like many organs throughout the body, the kidneys and the bladder are composed of an innermost single layer epithelium, which is referred to as the urothelium in the bladder and ureters.

The kidney is a specialized organ that is designed to eliminate waste products. The major functional unit within the kidney is the nephron. Within nephrons are duct systems called renal tubules, within which the transport of waste out of the blood and reabsorption of water and other nutrients occurs, resulting in the formation of urine. The epithelial layer lining the proximal tubule is polarized, which means that it possesses distinct apical (lumen-facing) and basolateral (basement membrane-facing) surfaces, which allows these cells to perform their transport functions. A polarized membrane is dependent on tight junctions, protein complexes that connect adjacent cells together and prevent transport of molecules between cells, performing a barrier function that “tightens” the monolayer.

To mimic this polarity in vitro, researchers have developed specialized membranes called transwells. Cells seeded on transwells are raised above the bottom plastic of the cell culture dish and therefore, have distinct apical and basal media. Once cells reach confluency, they form a monolayer and begin to polarize, which can be monitored using a measurement called transepithelial electrical resistance (TEER), which measures the “tightness” of the monolayer and the efficiency of the tight junctions.

A Study of Renal Epithelial Cell Tight Junctions

Recently, a new study was conducted by Gildea et al., who used our renal proximal tubule cells and RenaLife™ media to study the effects of a new dietary supplement on epithelial cell tight junctions. Like the renal tubules, the intestinal tract also contains a polarized epithelial monolayer that is held together by tight junctions. One of the dietary molecules that affects tight junctional integrity is PT-gliadin, a component of the gluten protein. Individuals with celiac disease experience an autoimmune reaction to gliadin, which disrupts tight junctions, making them less tight and causing increased intestinal permeability, or abnormal transport between adjacent cells in the intestinal monolayer. To help treat this tight junction dysregulation, a number of dietary supplements have been developed.

In a 2016 study, Gildea et al. investigated the effects of RESTORE, a dietary supplement that is derived from lignite (also known as brown coal, or fossil soil). The researchers used an in vitro model of polarized intestinal cells and Lifeline® primary human renal proximal tubule cells grown on transwells to induce polarization, and measured the effects of RESTORE on tight junctional integrity by measuring transepithelial electrical resistance (TEER). They found that RESTORE increased TEER in IEC-6 and Caco-2 intestinal cells, indicating improved tight junction function. In contrast, treatment with PT-gliadin decreased TEER, indicating reduced tight junction function. Importantly, RESTORE reversed the effect of PT-gliadin on TEER, protecting epithelial cells from loss of tight junction function, confirmed by immunofluorescent imaging for the tight junction protein ZO1. Finally, the researchers found that RESTORE decreased apoptosis in Lifeline® renal proximal tubule cells. Together, their results suggest that RESTORE, and potentially other lignite-derived compounds, is effective at protecting against gliadin-induced tight junction disruption.

Lifeline® Bladder and Renal Epithelial Cells

The Lifeline® catalog of bladder and renal cells includes:

Lifeline® normal human bladder epithelial and renal epithelial cells are optimized for growth in UroLife™ and RenaLife™ media.  We have also introduced a new medium for culturing bladder dome and apex epithelial cells: UroLife® Medium Complete Kit (LL-0071). Our bladder and renal epithelial cells have been used as normal control cells in studies that investigate the toxicity of potential therapeutic compounds, both natural and synthetic. In these studies, the compound selectively affected the cancer cell type being investigated, while leaving Lifeline® normal cells unaffected. Our bladder and renal epithelial cells have also been used to study cell cycle arrest, induction of apoptosis, and investigate new therapies to protect against kidney damage or regenerate damaged kidney tissue.

If you are using Lifeline® cell types or media, please let us know! We are always interested in learning the new ways our customers are using our products to answer their research questions!