Methylglyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Inflammation via Interaction with RAGE in Mesangial Cells

Introduction Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) mediate renal function during diabetic and non-diabetic nephropathy development. Methylglyoxal-lysine dimer (MOLD), a typical toxic advanced glycation end product (TAGE), contributes to inflammatory responses during renal diseases. This study determines the effect of MOLD on inflammatory responses in mouse mesangial cells. Methods and Results The murine mesangial cell line SV40 MES 13 is used to assess nuclear factor-kappa B (NF-kappa B) expression, reactive oxygen species (ROS) production, and mitochondria labeling. The interaction model between RAGE and MOLD is also determined. MOLD treatment of mesangial cells markedly increases RAGE expression and the linkage with V-type Ig domain of RAGE. MOLD induces ROS production and mitochondrial dysfunction. MOLD activates phosphatidylinositol 3-kinase-protein kinase B (PI3KB) and NF-kappa B signaling pathways. It is confirmed that these changes are reversed when ROS is suppressed. These effects may be regulated through mitogen-activated protein kinases and pro-inflammatory cytokines in circulatory inflammation responses. Conclusion MOLD plays a major role in nephropathy via ROS production and mitochondrial dysfunction through direct association with RAGE. Further, the NF-kB and PI3K/AKT signaling pathways triggered by ROS mediate the inflammatory response to exacerbate MOLD-induced damages in inflammation-related diabetic and non-diabetic renal diseases.

Automated summary

The study found that MOLD significantly increases RAGE expression in mouse mesangial cells, leading to ROS production and mitochondrial dysfunction. MOLD activates PI3KB and NF-kappa B signaling pathways, triggering inflammatory responses.