Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages

作者：Huang, Xiaoxia; Li, Bingyu; Hu, Jiaqing; Liu, Zhuanhua; Li, Dongping; Chen, Zhenfeng; Huang, Hang; Chen, Yanjia; Guo, Xiaohua; Cui, Yun^*; Huang, Qiaobing^*

来源：Frontiers in Physiology, 2022, 13: 977247.

DOI：10.3389/fphys.2022.977247

• advanced glycation endproducts
• RAGE
• angiogenesis
• renal fibrosis
• moesin phosphorylation

Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. In WT mice treated with AGE-modified bovine serum albumin (AGE-BSA), distinct abnormal angiogenesis in Bowman's capsule of the kidney emerged early after 1 m under AGE-BSA stimulation, while these neovessels became rare after 6 m. AGE-BSA also induced glomerular hypertrophy and mesangial expansion at 1 m but glomerular atrophy and fibrosis at 6 m. Electron microscopy imaging demonstrated the damage of foot process integrity in podocytes and the uneven thickening of the glomerular basement membrane in the AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with these AGE-induced morphological changes. However, these AGE-BSA-induced pathological changes were significantly attenuated in RAGE-knockout mice. Moreover, moesin phosphorylation was accompanied by AGE-BSA-induced alterations and moesin deficiency in mice attenuated by AGE-BSA-induced fibrosis. The investigation on glomerular endothelial cells (GECs) also confirmed that the phosphorylation of moesin T558 is critical in AGE-induced tube formation. Overall, this study suggests that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation.

• 单位
  南方医科大学; 1; y