| First Author | Esposito V | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 4 | Pages | F440-50 |
| PubMed ID | 23235477 | Mgi Jnum | J:193184 |
| Mgi Id | MGI:5467875 | Doi | 10.1152/ajprenal.00487.2011 |
| Citation | Esposito V, et al. (2013) CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury. Am J Physiol Renal Physiol 304(4):F440-50 |
| abstractText | 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-alpha 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-kappaB 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. |
