Advanced Glycation Endproducts Stimulate Renal Epithelial Cells to Release Chemokines That Recruit Macrophages, Leading to Renal Fibrosis

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  • SASAI Yosuke
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • IWAKAWA Kousei
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • YANAGIDA Kanako
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • SHEN Yan
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • HOSONO Takashi
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • ARIGA Toyohiko
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences
  • SEKI Taiichiro
    Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences

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Diabetic nephropathy is a major complication of diabetes and tubulointerstitial fibrosis is one of its manifestations. This study aimed to clarify the pathogenicity of advanced glycation endproducts (AGEs) toward NRK-52E, a tubular epithelial cell line. The AGE-exposed cells significantly increased gene expression of transforming growth factor beta, plasminogen activator inhibitor-1, and tissue transglutaminase, and a medium conditioned by them showed strong potential to recruit macrophages, partly through a chemokine, monocyte chemoattractant protein-1. Albumin denatured by maintenance at 37 °C for 120 d exhibited similar activities, but they were lower than those of the AGEs. Thus, AGEs generated in diabetic patients might exacerbate fibrosis in the kidneys directly through renal epithelial cell stimulation, and indirectly by recruitment of macrophages.

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