Methylglyoxal-derived advanced glycation end products induce matrix metalloproteinases through activation of ERK/JNK/NF-κB pathway in kidney proximal epithelial cells
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The accumulation of reactive α-dicarbonyl leading to advanced glycation end products (AGEs) have been linked to pathophysiological diseases in many studies, such as atherosclerosis, cataract, cancer, and diabetic nephropathy. Glycation-generated AGEs increase the expression of inflammatory cytokines by transferring signals to the cell by binding them to the receptor for AGEs (RAGE) on their cell surface. The effect of methylglyoxal-derived AGEs (AGE-4) on the induction of matrix metalloproteinases (MMPs) in rat ordinary kidney cells (NRK-52E) was explored in this research, among other AGEs. The cell treated with 100 μg/mL AGE-4 for 24 h showed a substantial rise in MMP-2 and MMP-9 expression relative to BSA control only and other AGEs through ERK, JNK, and NF-B pathways. Our findings therefore suggest that AGE-4 expresses MMPs through the AGE-4-RAGE axis, activating MAPK signals that may contribute to dysfunction of the kidney cell.
KeywordsAdvanced glycation end products Diabetic nephropathy Matrix metalloproteinase MAPK NF-κB
This study was supported by Main Research Program (E0164400-04) of the Korea Food Research Institute (KFRI) funded by the Ministry of Science, ICT and Future Planning, the National Research Foundation of Korea grant funded by the Korea government (MEST) (No. 2017R1A2B4012182), Korea University Research Grant No. K1516071, and School of Life Sciences and Biotechnology of Korea University for BK21 PLUS. The authors are grateful to the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for allowing access to their equipment and facilities.
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Conflict of interest
The authors have no conflict of interest to declare.
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