title: Advanced glycation endproducts stimulate renal epithelial cells to release chemokines that recruit macrophages, leading to renal fibrosis.
abstract: 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.
authors.affiliation: Laboratory of Nutrition and Physiology, Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sasai
authors.forename: Kousei
authors.initials: K
authors.lastname: Iwakawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Yanagida
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosono
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D015194:Diffusion Chambers, Culture; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D017127:Glycation End Products, Advanced; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D011503:Transglutaminases