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- Title
Endoplasmic reticulum stress participates in inflammation-accelerated, lipid-mediated injury of human glomerular mesangial cells.
- Authors
Yang, Haiping; Cui, Jingjing; Shi, Jing; Yang, Baohui; Wang, Mo; Wu, Daoqi; Zhang, Gaofu; Liu, Wei; Li, Qiu
- Abstract
Aim 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. Conclusion 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.
- Subjects
KIDNEY glomerulus diseases; ENDOPLASMIC reticulum; LOW density lipoproteins; INFLAMMATION; LIPIDS
- Publication
Nephrology, 2017, Vol 22, Issue 3, p234
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/nep.12748