| First Author | Sassi A | Year | 2020 |
| Journal | J Am Soc Nephrol | Volume | 31 |
| Issue | 5 | Pages | 1009-1023 |
| PubMed ID | 32245797 | Mgi Jnum | J:321864 |
| Mgi Id | MGI:6871714 | Doi | 10.1681/ASN.2019080790 |
| Citation | Sassi A, et al. (2020) Interaction between Epithelial Sodium Channel gamma-Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct. J Am Soc Nephrol 31(5):1009-1023 |
| abstractText | BACKGROUND: Water and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient. METHODS: To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule-specific knockout mice lacking ENaC subunits to assess the ENaC's effect on claudin-8 expression. RESULTS: Overexpression or silencing of the ENaC gamma-subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule-specific ENaC gamma-subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC beta-subunit or alpha-subunit silencing or kidney tubule-specific beta-ENaC or alpha-ENaC knockout mice did not alter claudin-8 abundance. CONCLUSIONS: Our data reveal the specific coupling between ENaC gamma-subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability. |
