...
首页> 外文期刊>Endocrinology, Diabetes & Metabolism >The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion (alters structural composition)
【24h】

The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion (alters structural composition)

机译:年龄受体,OST48驱动Podocyte足处理效果和基底膜膨胀(改变结构组合物)

获取原文
           

摘要

Aims The accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno-protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno-protection. Materials and methods To examine the effects of increased podocyte oligosaccharyltransferase-48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase-48kDa subunit abundance in podocytes driven by the podocin promoter. Results Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra-resolution microscopy of podocytes revealed denudation of foot processes where there was co-localization of oligosaccharyltransferase-48kDa subunit and advanced glycation end-products. Conclusions These studies indicate that increased podocyte expression of oligosaccharyltransferase-48?kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.
机译:目的是先进的糖化末端产品的积累涉及糖尿病肾病的开发和进展。没有研究通过受体操纵刺激先进的糖化清除是在糖尿病中的肾脏保护性。足细胞是糖尿病肾疾病的早期贡献者,可以是人工保护的目标。材料和方法检测多细胞寡核苷酸转移酶-48对肾功能的影响,肾小球硬化,微管癖纤维化和蛋白质组(PXD011434),我们产生了由Podocin启动子驱动的寡核苷酸中的寡核糖酰基转移酶-48KDA亚基丰度的小鼠。结果尽管先进的糖化末端产品的尿液清除增加,但我们观察到肾功能下降,显着的肾小球损伤,包括肾小球粥样硬化,胶原蛋白沉积,肾小球基底膜增厚和足部工艺侵蚀和微管间纤维化。与胶原沉积,内质网应力和氧化应激相关的蛋白质中鉴定孤立的肾小球分析。多粒细胞的超分辨率显微镜揭示了少量定位寡核糖酸酶-48KDA亚基和先进的糖糖末端产物的脚踏过程的剥蚀过程。结论这些研究表明,寡核苷酸转移酶-48的泛细胞表达增加,kda亚基的表达导致肾小球内质子胁迫和肾功能下降。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号