CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury

Vittoria Esposito, Fabrizio Grosjean, Jianming Tan, Liangfu Huang, Libing Zhu, Jian Chen, Huabao Xiong, Gary E. Striker, Feng Zheng

Research output: Contribution to journalArticle

Abstract

C/EBP homologous protein (CHOP) is an important mediator of endoplasmic reticulum (ER) stress-induced cell and organ injury. Here we show that lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with ER stress and elevated CHOP. We postulated that CHOP-/- mice would be protected against LPS-induced-AKI. Unexpectedly, while Toll-like receptor 4 (TLR4) expression levels were comparable in kidneys of CHOP-/- and wild-type (WT) mice, CHOP-/- mice developed more severe AKI after LPS injection. Furthermore, the severe kidney injury in CHOP-/- mice was associated with an exaggerated inflammatory response. Serum TNF-α levels were more elevated in LPS-treated CHOP-/- mice. There was a 3.5-fold higher amount of renal neutrophil infiltrates in LPS-treated CHOP-/- than in WT mice. Additionally, the kidneys of LPS-treated CHOP-/- mice had a more prominent increase in NF-κB activation and further upregulation of proinflammatory genes, i.e., c-x-c motif ligand 1 (CXCL-1), macrophage inflammatory protein-2 (MIP-2), and IL-6. Finally, proximal tubules, glomeruli, and podocytes isolated from CHOP-/- mice also had an exaggerated proinflammatory response to LPS. Since LPS directly increased CHOP in glomeruli and podocytes of WT mice, together these data suggest that the LPSinduced increase of CHOP in kidneys may inhibit inflammatory response in renal cells and provide protection against AKI.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume304
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

Keywords

  • CHOP
  • ER stress
  • Glomeruli
  • Inflammation
  • Podocytes
  • Proximal tubules

ASJC Scopus subject areas

  • Physiology
  • Urology

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