title: Endoplasmic reticulum stress participates in inflammation-accelerated, lipid-mediated injury of human glomerular mesangial cells.
abstract: OBJECTIVE
  The mechanism of lipid-mediated injury of human glomerular mesangial cells (HMCs) remains unclear. We investigated the association between endoplasmic reticulum (ER) stress and lipid-mediated injury in HMCs in vitro and the potential efficacy of a therapeutic approach targeting ER stress.
  
  
  METHODS
  Human glomerular mesangial cells were exposed to low-density lipoprotein (LDL) and/or interleukin-1β (IL-1β). For evaluation of whether ER stress participates in lipid-mediated injury to HMCs, HMCs were pretreated with tunicamycin or treated with sodium 4-phenylbutyrate (4-PBA).
  
  
  RESULTS
  Incubation of HMCs with LDL + IL-1β significantly increased lipid accumulation and induced phenotypic changes. ER stress was induced in lipid-loaded HMCs, as indicated by upregulation of glucose-regulated protein 78 (GRP78) and protein kinase RNA-like ER kinase (PERK) proteins. Moreover, persistent ER stress increased expression of nuclear factor (NF)-κB p65 protein, fibronectin, and α-smooth muscle actin (α-SMA) mRNA partly through the PERK - eukaryotic initiation factor-2α (eIF2α) pathway. Preconditioning with ER stress by tunicamycin and inhibition of ER stress by 4-PBA both reversed the phenotypic changes and decreased lipid accumulation and inflammatory cytokine secretion by the PERK - eIF2α pathway.
  
  
  CONCLUSIONS
  These data provide evidence that ER stress participates in inflammation associated with lipid-induced injury of HMCs. Modulation of ER stress may be a novel therapeutic approach for combating lipid-induced injury of HMCs.
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Daoqi
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Gaofu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Nephroimmunology, Key Laboratory of the Ministry of Education, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
mesh_terms: D018929:Cell Culture Techniques; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000009:adverse effects*; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases
keywords: endoplasmic reticulum stress; human glomerular mesangial cells; inflammation; lipid accumulation