title: Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products.
abstract: Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increases lipid accumulation in a human renal tubular epithelial cell line (HK-2) via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR), followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr) mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.
authors.affiliation: Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Zilin
authors.initials: Z
authors.lastname: Sun
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects*; D000071518:Liver X Receptors / Q000378:metabolism; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D017127:Glycation End Products, Advanced; D000071518:Liver X Receptors; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; C048496:N(6)-carboxymethyllysine; D002784:Cholesterol; D008239:Lysine