Renal atrophy after ischemia–reperfusion injury depends on massive tubular apoptosis induced by TNFα in the later phase
- 10 January 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Medical Molecular Morphology
- Vol. 47 (4), 213-223
- https://doi.org/10.1007/s00795-013-0067-3
Abstract
Recent studies have suggested that acute kidney injury (AKI) develops into chronic kidney disease (CKD). However, a mechanism for disease progression from AKI to CKD has not been established. We developed two ischemia–reperfusion injury (IRI) mouse models, a repaired kidney model and an atrophic kidney model, and studied the mechanisms of renal atrophy after IRI by comparing the two models. We found that renal atrophy after IRI depended on tubular apoptosis at 14 days after IRI. Moreover, we found that Tnfα and FasL mRNA were synchronously expressed at the time of tubular apoptosis. To elucidate the relationship between tubular apoptosis and apoptotic ligands, we administered TNFα and FasL neutralizing antibodies according to the time of tubular apoptosis. TNFα blockade significantly repressed tubular apoptosis, resulting in the prevention of renal atrophy. FasL blockade could not repress tubular apoptosis, resulting in renal atrophy. We also found that TNF receptors were expressed in the kidney at 14 days after IRI, but Fas receptor was not. We concluded that renal atrophy after IRI depends on tubular apoptosis induced by the TNFα signaling pathway in the later phase of renal IRI, and that TNFα blockade could be a potential new therapeutic approach for improving renal prognosis after AKI.Keywords
This publication has 41 references indexed in Scilit:
- Outpatient Nephrology Referral Rates after Acute Kidney InjuryJournal of the American Society of Nephrology, 2012
- Cellular pathophysiology of ischemic acute kidney injuryJCI Insight, 2011
- The severity of acute kidney injury predicts progression to chronic kidney diseaseKidney International, 2011
- Blocking Fas Ligand on Leukocytes Attenuates Kidney Ischemia-Reperfusion InjuryJournal of the American Society of Nephrology, 2011
- Renal tubular Fas ligand mediates fratricide in cisplatin-induced acute kidney failureKidney International, 2011
- Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney diseaseKidney International, 2009
- Long-term Risk of Mortality and Other Adverse Outcomes After Acute Kidney Injury: A Systematic Review and Meta-analysisAmerican Journal of Kidney Diseases, 2009
- Prevention of Renal Ischemic Injury by Silencing the Expression of Renal Caspase 3 and Caspase 8Transplantation, 2006
- TNFR1‐ and TNFR2‐mediated signaling pathways in human kidney are cell type‐specific and differentially contribute to renal injuryThe FASEB Journal, 2005
- TNF receptor-associated factor-2 binding site is involved in TNFR75-dependent enhancement of TNFR55-induced cell deathCell Research, 2001