Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Toxicology. 2024 Sep;507:153887. doi: 10.1016/j.tox.2024.153887. Epub 2024 Jul 15.
Advanced glycation end products (AGEs) are important contributors to the progression of chronic kidney diseases (CKD), including renal fibrosis. Although the relationship between AGEs and renal fibrosis has been well studied, the mechanisms of individual AGE-induced renal injury remain poorly understood. This study investigated the adverse effect of methylglyoxal-derived hydroimidazolone-1 (MG-H1), a methylglyoxal (MG)-derived AGE generated by the glycation of MG and arginine residues, on kidney damage. We aimed to elucidate the molecular mechanisms of MG-H1-mediated renal injury and fibrosis, focusing on the receptor for AGEs (RAGE) signaling and its effects on the Wnt/β-catenin pathway, MAPK pathway, and inflammatory responses. Our results suggest that the MG-H1/RAGE axis plays a significant role in the pathogenesis of CKD and its downstream events involving MAPK kinase-related factors and inflammatory factors. MG-H1 treatment modulated the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and MAPK proteins (ERK1/2, JNK, and p38).
晚期糖基化终产物（AGEs）是慢性肾脏病（CKD）进展的重要因素，包括肾纤维化。虽然 AGEs 与肾纤维化之间的关系已得到充分研究，但个体 AGE 诱导的肾损伤的机制仍知之甚少。本研究探讨了甲基乙二醛衍生的羟咪唑啉-1（MG-H1），一种由甲基乙二醛（MG）和精氨酸残基糖化产生的 MG 衍生的 AGE，对肾脏损伤的不良影响。我们旨在阐明 MG-H1 介导的肾损伤和纤维化的分子机制，重点关注 AGEs 受体（RAGE）信号及其对 Wnt/β-catenin 途径、MAPK 途径和炎症反应的影响。我们的结果表明，MG-H1/RAGE 轴在 CKD 的发病机制及其下游事件中发挥重要作用，涉及 MAPK 激酶相关因子和炎症因子。MG-H1 处理调节了炎症细胞因子（TNF-α、IL-6 和 IL-1β）和 MAPK 蛋白（ERK1/2、JNK 和 p38）的表达。
