Abstract | BACKGROUND: We previously demonstrated that chronic hypoxia has pivotal roles in the progression of tubulointerstitial injury from the early stage of the uninephrectomized Thy1 nephritis model. We have also shown that pretreatment of cobalt confers renoprotection in the ischemia/reperfusion (I/R) injury, in association with the up-regulation of hypoxia-inducible factor (HIF)-regulated genes. Here, we tested the hypothesis that cobalt administration not only attenuates acute ischemic insult, but also ameliorates tubulointerstitial injury secondary to chronic hypoxia. METHODS: RESULTS: Although the intervention did not change glomerular structural damage or urinary protein excretion rate, tubulointerstitial injury was improved in cobalt-treated animals when compared with the vehicle-treated group. The amelioration was associated with the parallel up-regulation of renoprotective, HIF-regulated gene expression. TUNEL staining revealed that the number of apoptotic cells was reduced in the cortex by cobalt administration, suggesting that renoprotection was achieved partly through its antiapoptotic properties. Furthermore, it was demonstrated that cobalt treatment exerts additional renoprotective effects with the ARB treatment in this model. CONCLUSION: Maneuvers to activate HIF in the ischemic tubulointerstitium will be a new direction to future therapeutic strategies.
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Authors | Tetsuhiro Tanaka, Makiko Matsumoto, Reiko Inagi, Toshio Miyata, Ichiro Kojima, Takamoto Ohse, Toshiro Fujita, Masaomi Nangaku |
Journal | Kidney international
(Kidney Int)
Vol. 68
Issue 6
Pg. 2714-25
(Dec 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 16316346
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Antimutagenic Agents
- Hypoxia-Inducible Factor 1
- Isoantibodies
- Vascular Endothelial Growth Factor A
- anti-Thy antibody
- Erythropoietin
- Cobalt
- Heme Oxygenase-1
- cobaltous chloride
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Topics |
- Animals
- Antibodies
(pharmacology)
- Antimutagenic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Capillaries
(pathology)
- Cobalt
(pharmacology)
- Erythropoietin
(genetics)
- Gene Expression Regulation
(drug effects)
- Glomerulonephritis
(drug therapy, pathology, physiopathology)
- Glomerulosclerosis, Focal Segmental
(drug therapy, pathology, physiopathology)
- Heme Oxygenase-1
(genetics)
- Hypoxia
(drug therapy, pathology, physiopathology)
- Hypoxia-Inducible Factor 1
(metabolism)
- In Situ Nick-End Labeling
- Isoantibodies
- Kidney Tubules
(pathology)
- Male
- Nephrectomy
- Rats
- Rats, Sprague-Dawley
- Renin-Angiotensin System
(drug effects)
- Reperfusion Injury
(drug therapy, pathology, physiopathology)
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors, genetics, immunology)
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