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.

Genome-wide association study of IgA nephropathy using 23 465 microsatellite markers in a Japanese population

“…We performed immunohistochemistry for tetraspanin-8 on human renal biopsy specimens associated with IgAN. 31 In this study, we found that tetraspanin-8 was often expressed in vascular smooth muscle cells and occasionally in tubule cells in normal kidneys, and the degree of tubular staining negatively correlated with the estimated glomerular filtration rate, independently of the type of nephropathy. 31 Further studies are needed to clarify the molecular mechanism underlying the tetraspanin-mediated development of IgAN.…”

“…31 In this study, we found that tetraspanin-8 was often expressed in vascular smooth muscle cells and occasionally in tubule cells in normal kidneys, and the degree of tubular staining negatively correlated with the estimated glomerular filtration rate, independently of the type of nephropathy. 31 Further studies are needed to clarify the molecular mechanism underlying the tetraspanin-mediated development of IgAN. Furthermore, studies are required to elucidate their function in the pathogenesis or progression of the disease due to interactions between Tspan8 and CD151 as a risk for IgAN.…”

Identification of cold responsive genes in Pacific white shrimp (Litopenaeus vannamei) by suppression subtractive hybridization

“…Still another role for TSPAN8 is seen during kidney disease in Humans; where TSPAN8 is believed serve a protective role (Pan et al). TSPAN8 may also provide protection during cold stress by forming membrane microdomains with other proteins to maintain membrane cryostability and fluidity, which is essential for resisting low temperature stress (Champy et al;Hirukawa et al;Cossins and Prosser, 1978).…”

The role of Tetraspanins in digestive system tumor development: update and emerging evidence

“…Tspan8 is also expressed in the stomach and duodenum, and it is required for acinar, gastric, and duodenal development ( Jarikji et al, 2009 ). Enhanced Tspan8 expression identified in injured distal tubules of the kidney may contribute to tubule repair by facilitating migration and invasion of tubule cells ( Hirukawa et al, 2014 ). Moreover, Tspan8 is expressed in the hippocampus and cerebellum of the brain, and participates in the development and maintenance of neuronal circuits through regulation of the expression of downstream genes, such as neurotrophic receptor tyrosine kinase 2 ( Schartner et al, 2017 ).…”