The role of LIGHT in the pathogenesis of glomerulonephritis

光在肾小球肾炎发病机制中的作用

• 批准号: 20790602
• 负责人: UEDA Hiroyuki
• 金额: $ 2.08万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790602/
• 关键词: LIGHT; IgA腎症; LTbeta受容体; HVEM受容体; 半月体形成性腎炎; LT-β受容体; HVEM; LT-ss受容体

LIGHT, a member of TNF superfamily, has been reported to play a important role for costimulatory molecules in T cell activation and expansion. Previous studies have shown that treatment of rodents with a lymphotoxin (LT) beta receptor-Ig fusion protein (LTbetaR-Ig), which binds to both LT and LIGHT, prevents the development of Tcell-mediated autoimmune diseases. In addition, dysregulated T cell-derived LIGHT lead to pathological features similar to those of human IgA nephropathy (IgAN). These data raise the possibility that LIGHT is involved in the pathogenesis of glomerulonephritis, e.g, IgAN or crescentic glomerulonephritis. The aim of this study is to explore the involvement of LIGHT in the pathogenisis of glomerulonephritis by using experimental autoimmune anti-glomerular basement membranenephritis (EAG) or murin IgA nephropathy model. For this purpose, we generated LTbetaR-Ig and verified whether LTbetaR-Ig treatment prevents EAG induced in WKY rats by immunization with an nephritogenic peptide, recombinant alpha 3(IV)NC1 of type IV collagen. Rats injected with nephritogenic antigen showed heavy proteinuria and crescent formation in 80 to 100% of the glomeruli as shown previously, but there was no significant difference between LTbetaR-Ig-treament and non-treatment groups in our study.

LIGHT是肿瘤坏死因子超家族成员之一，已被报道在T细胞活化和扩增过程中发挥重要的共刺激分子作用。先前的研究表明，用淋巴毒素(LT)β受体-Ig融合蛋白(LTbetaR-Ig)治疗啮齿动物，它与LT和LIGH结合，可以防止T细胞介导的自身免疫性疾病的发展。此外，调节失调的T细胞来源的光导致类似于人类IgA肾病(IgAN)的病理特征。这些数据增加了LIGH参与肾小球肾炎发病机制的可能性，例如，IgAN或新月体肾炎。本研究通过建立自身免疫性抗肾小球基底膜肾炎(EAG)或鼠IgA肾病模型，探讨LIGH在肾炎发病机制中的作用。为此，我们制备了LTbetaR-Ig，并验证了LTbetaR-Ig治疗是否能阻止致肾病多肽--重组IV型胶原α3(IV)Nc1免疫WKY大鼠诱发的EAG。如前所述，注射致肾性抗原的大鼠肾小球80%~100%出现大量蛋白尿和新月体形成，但LTbetaR-Ig治疗组与非治疗组无显著差异。

项目成果

PGN I型様糸球体病変を合併したIgA-κ型多発性骨髄腫(MM)の一例

IgA-κ型多发性骨髓瘤（MM）并发PGN I型样肾小球病变1例

• 发表时间: 2009
• 作者: 上田裕之;神崎剛;大塚泰史;栗山哲;宮崎陽一;宇都宮保典;川村哲也;細谷龍男
• 通讯作者: 細谷龍男

腎臓病診療ゴールデンハンドブック

肾病治疗黄金手册

• 发表时间: 2009
• 作者: 上田裕之;神崎剛;大塚泰史;栗山哲;宮崎陽一;宇都宮保典;川村哲也;細谷龍男;栗山哲編
• 通讯作者: 栗山哲編

Successful effect of triple blockade of renin-angiotensin-aldosterone system on massive proteinuria in a patient with chronic kidney disease

• DOI: 10.1007/s10157-009-0213-3
• 发表时间: 2009-12-01
• 期刊: CLINICAL AND EXPERIMENTAL NEPHROLOGY
• 影响因子: 2.3
• 作者: Kuriyama, Satoru;Sugano, Naoki;Hosoya, Tatsuo
• 通讯作者: Hosoya, Tatsuo