| First Author | Rickman OJ | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 3 | PubMed ID | 38171596 |
| Mgi Jnum | J:344178 | Mgi Id | MGI:7571891 |
| Doi | 10.26508/lsa.202302304 | Citation | Rickman OJ, et al. (2024) Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport. Life Sci Alliance 7(3) |
| abstractText | The mouse cortical collecting duct cell line presents a tight epithelium with regulated ion and water transport. The epithelial sodium channel (ENaC) is localized in the apical membrane and constitutes the rate-limiting step for sodium entry, thereby enabling transepithelial transport of sodium ions. The membrane-bound serine protease Tmprss2 is co-expressed with the alpha subunit of ENaC. alphaENaC gene expression followed the Tmprss2 expression, and the absence of Tmprss2 resulted not only in down-regulation of alphaENaC gene and protein expression but also in abolished transepithelial sodium transport. In addition, RNA-sequencing analyses unveiled drastic down-regulation of the membrane-bound protease CAP3/St14, the epithelial adhesion molecule EpCAM, and the tight junction proteins claudin-7 and claudin-3 as also confirmed by immunohistochemistry. In summary, our data clearly demonstrate a dual role of Tmprss2 in maintaining not only ENaC-mediated transepithelial but also EpCAM/claudin-7-mediated paracellular barrier; the tight epithelium of the mouse renal mCCD cells becomes leaky. Our working model proposes that Tmprss2 acts via CAP3/St14 on EpCAM/claudin-7 tight junction complexes and through regulating transcription of alphaENaC on ENaC-mediated sodium transport. |
