In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 304, No. 4 ( 2013-02-15), p. F440-F450
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 LPS-induced increase of CHOP in kidneys may inhibit inflammatory response in renal cells and provide protection against AKI.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00487.2011
Language:
English
Publisher:
American Physiological Society
Publication Date:
2013
detail.hit.zdb_id:
1477287-5
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