Kidney Diseases Enhance Expression of Tetraspanin-8: A Possible Protective Effect against Tubular Injury

Abstract

Background/Aims:TSPAN8 encoding tetraspanin-8 was identified as a candidate gene for immunoglobulin A nephropathy (IgAN) by a genome-wide association study using microsatellites in the Japanese population. Tetraspanin-8 is a cell surface protein that contributes to the migration and invasion of epithelial cells. Methods: We performed immunohistochemistry for tetraspanin-8 on human renal biopsy specimens associated with IgAN, antineutrophil cytoplasmic antibody-associated nephropathy and interstitial nephritis, as well as normal renal tissue. Furthermore, to study the potential function of tetraspanin-8, we performed cell migration and invasion assays using human renal tubule cells transfected with tetraspanin-8. Results: Tetraspanin-8 was often expressed in vascular smooth muscle cells and occasionally in tubule cells in normal kidney. In the kidneys of all types of nephropathy, tetraspanin-8 staining in the arteries was unaffected, but that in the tubules was enhanced. The degree of tubular staining negatively correlated with the estimated glomerular filtration rate, independently of the type of nephropathy. Tetraspanin-8-expressing tubule cells were found predominantly in distal and collecting tubules, identified by cytokeratin 7 or aquaporin 2 staining. In vitro studies using cultured tubule cells revealed that tetraspanin-8 promoted migration by 2.7-fold without laminin, by 2.8-fold with laminin and invasion into Matrigel by 3.5-fold, suggesting that enhanced tetraspanin-8 may be involved in the repair of tubules. Conclusion: The obtained findings indicate that tetraspanin-8 expression is enhanced in injured distal tubules, which may be involved in the repair of tubules by facilitating migration and invasion.