title: High Glucose Enhances oxLDL-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells Largely via Inducing Lectin-Like ox-LDL Receptor-1.
abstract: BACKGROUND
  High blood glucose is characteristic of diabetic nephropathy (DN). Both lectin-like ox-LDL receptor-1 (LOX-1) and renal tubular epithelial cells apoptosis reportedly are important for the pathogenesis and progression of DN. In this study, we explored the regulatory effects of high glucose on the expression of LOX-1 and its impact on oxLDL-induced apoptosis in human renal proximal tubular epithelial cells (HRPTEpCs).
  
  
  METHODS
  Primary HRPTEpCs were treated with high glucose with or without concurrent treatment with selective p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 or lentiviral knockdown of LOX-1. HRPTEpCs cultured in normal glucose concentration (5.5 mmol/l) was used as a control.
  
  
  CONCLUSIONS
  High glucose concentration dependency increased the expression of LOX-1, which led to increased ox-LDL binding in HRPTEpCs. In addition, high glucose upregulated the LOX-1 gene promoter activity but not its mRNA stability in HRPTEpCs; the effect was abolished by PD169316. Furthermore, high glucose markedly enhanced oxLDL-induced apoptosis in HRPTEpCs, which was largely abolished by knockdown of LOX-1. This study demonstrates that high glucose induces the expression of LOX-1 at the gene promoter/transcription level mainly by a p38 MAPK-dependent mechanism, which enhances oxLDL-induced apoptosis in renal tubular epithelial cells. It adds new insights into the molecular mechanisms underlying DN.
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Ruihong
authors.initials: R
authors.lastname: Liu
authors.forename: Shaobin
authors.initials: S
authors.lastname: Duan
authors.forename: Guxiang
authors.initials: G
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D007093:Imidazoles; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D034741:RNA, Small Interfering; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; D005947:Glucose