Alternative Titleシンビンディンの発現低下がスリット膜の機能障害に関与している
Synbindin in podocytes
Note (General)Introduction: Synbindin, originally identified as a neuronal cytoplasmic molecule, was found in glomeruli. cDNA subtractive hybridization technique showed the mRNA expression of synbindin in glomeruli was down-regulated in puromycin aminonucleoside (PAN) nephropathy, a mimic of minimal-change nephrotic syndrome. Methods: The expression of synbindin in podocyte was analyzed in normal rats and two types of rat nephrotic models, anti-nephrin antibody (ANA)-induced nephropathy a pure slit diaphragm injury model and PAN nephropathy by immunohistochemical analysis and RT-PCR techniques. To elucidate the function of synbindin, a gene silencing study with human cultured podocytes was performed. Results: Synbindin was mainly expressed at slit diaphragm area of glomerular epithelial cells (podocytes). In both nephrotic models, decreased mRNA expression and the altered staining of synbindin were already detected at the early phase when proteinuria and the altered staining of nephrin, a key molecule of slit diaphragm, were not detected yet. Synbindin staining was clearly reduced when severe proteinuria was observed. When the cultured podocytes were treated with siRNA for synbindin, the cell changed to be round-shape, and filamentous actin structure was clearly altered. The expression of ephrin-B1, a transmembrane protein at slit diaphragm, was clearly lowered, and synaptic vesicle-associated protein 2B (SV2B) was upregulated in the synbindin knockdown cells. Conclusion: Synbindin participates in maintaining foot processes and slit diaphragm as a downstream molecule of SV2B-mediated vesicle transport. Synbindin downregulation participates in slit diaphragm dysfunction. Synbindin can be an early marker to detect podocyte injury.
American journal of nephrology. 2021, 52(8), 620-629.
新大院博(医)第1031号
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2022-06-05T18:01:14+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション