Hirukawa Takashi, Wu Qiong, Sawada Kaichiro, Matsusaka Taiji, Saka Sanae, Oka Akira, Hirawa Nobuhito, Umemura Satoshi, Kakuta Takatoshi, Endoh Masayuki, Inoko Hidetoshi, Ichikawa Iekuni, Fukagawa Masafumi
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Yokohama, Japan.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Nephron Extra. 2014 Apr 30;4(1):70-81. doi: 10.1159/000362451. eCollection 2014 Jan.
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.
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.
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.
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.
背景/目的：通过在日本人群中使用微卫星进行的全基因组关联研究，编码四跨膜蛋白8的TSPAN8被鉴定为免疫球蛋白A肾病（IgAN）的候选基因。四跨膜蛋白8是一种细胞表面蛋白，有助于上皮细胞的迁移和侵袭。
我们对与IgAN、抗中性粒细胞胞浆抗体相关性肾病和间质性肾炎相关的人类肾活检标本以及正常肾组织进行了四跨膜蛋白8的免疫组织化学检测。此外，为了研究四跨膜蛋白8的潜在功能，我们使用转染了四跨膜蛋白8的人肾小管细胞进行了细胞迁移和侵袭试验。
在正常肾脏中，四跨膜蛋白8常在血管平滑肌细胞中表达，偶尔在肾小管细胞中表达。在所有类型肾病的肾脏中，动脉中的四跨膜蛋白8染色不受影响，但肾小管中的染色增强。肾小管染色程度与估计的肾小球滤过率呈负相关，与肾病类型无关。通过细胞角蛋白7或水通道蛋白2染色鉴定发现，表达四跨膜蛋白8的肾小管细胞主要位于远端小管和集合小管。使用培养的肾小管细胞进行的体外研究表明，四跨膜蛋白8在无层粘连蛋白时促进迁移2.7倍，在有层粘连蛋白时促进迁移2.8倍，并促进向基质胶的侵袭3.5倍，这表明四跨膜蛋白8的增强可能参与肾小管的修复。
获得的研究结果表明，四跨膜蛋白8在受损的远端小管中表达增强，这可能通过促进迁移和侵袭参与肾小管的修复。
