AUTHOR=Huang Xiaoxia , Li Bingyu , Hu Jiaqing , Liu Zhuanhua , Li Dongping , Chen Zhenfeng , Huang Hang , Chen Yanjia , Guo Xiaohua , Cui Yun , Huang Qiaobing 

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

JOURNAL=Frontiers in Physiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.977247

DOI=10.3389/fphys.2022.977247

ISSN=1664-042X

ABSTRACT=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 AGEs 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 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 glomerular basement membrane in AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with those AGE-induced morphological changes. However, those AGE-BSA-induced pathological changes were significantly attenuated in RAGE knockout mice. Moreover, moesin phosphorylation was accompanied with those AGE-BSA-induced alterations and moesin deficiency in mice attenuated 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.