title: Advanced oxidation protein products induce hypertrophy and epithelial-to-mesenchymal transition in human proximal tubular cells through induction of endoplasmic reticulum stress.
abstract: BACKGROUND
  In chronic kidney disease (CKD), the accumulation of advanced oxidation protein products (AOPPs) is prevalent. Hypertrophy and epithelial-to-mesenchymal transition (EMT) of tubular cells are associated with the pathogenesis of CKD. However, whether AOPPs induce tubular-cell hypertrophy and EMT is unclear. In this study, we investigated the effect of AOPPs on human proximal tubular cells (HK-2 cells) and the mechanisms underlying tubular-cell hypertrophy and EMT in vitro.
  
  
  METHODS
  The mRNA and protein expression of CCAAT/enhancer-binding protein-homologous protein (CHOP), glucose-regulated protein (GRP) 78, p27, α-smooth muscle actin (α-SMA) and E-cadherin were evaluated by quantitative real-time PCR and western blot, respectively. Cell cycle was detected by flow cytometry. Bicinchoninic acid method was performed to measure total protein content.
  
  
  RESULTS
  AOPP treatment upregulated total protein expression, caused an increase in the percentage of G1-phase cells, and induced the overexpression of p27 and α-SMA, lowered the expression of E-cadherin. Furthermore, AOPP treatment induced the overexpression of GRP78 and CHOP. Moreover, the aforementioned effects were reversed following the treatment of cells with an NADPH oxidase inhibitor, a reactive oxygen species (ROS) scavenger, or salubrinal, which is an inhibitor of ER stress, whereas these effects were produced after exposure to thapsigargin, an inducer of ER stress.
  
  
  CONCLUSIONS
  Our results suggest that AOPPs induced HK-2-cell hypertrophy and EMT by inducing ER stress, which was likely mediated by ROS. These findings could facilitate the development of novel therapeutic strategies for suppressing the progression of CKD.
authors: Department of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
authors: Xun
authors: X
authors: Tang
authors: Guang
authors: G
authors: Rong
authors: Yang
authors: Y
authors: Bu
authors: Shaojie
authors: S
authors: Zhang
authors: Min
authors: M
authors: Zhang
authors: Jun
authors: J
authors: Zhang
authors: Xiujie
authors: X
authors: Liang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D062107:Advanced Oxidation Protein Products / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced* / Q000378:metabolism; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D062107:Advanced Oxidation Protein Products; D015820:Cadherins; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP