Activation of hypoxia-inducible factor by cobalt is associated with the attenuation of tissue injury and apoptosis in cyclosporine-induced nephropathy

The Tohoku Journal of Experimental Medicine
Se Won OhKi Young Na

Abstract

Hypoxia-inducible factor (HIF) is a transcription factor that regulates cellular hypoxic responses. Despite the therapeutic benefits of cyclosporine A (CsA) in organ transplantation, its clinical use is limited due to chronic nephropathy. We investigated whether HIF activation by cobalt could improve CsA-induced nephropathy, and investigated the related mechanism. In animal experiments, rats were kept on a 0.05% low-salt diet and administered CsA subcutaneously for 28 days (15 mg/kg/day). They also received cobalt (10 mg/kg/day) during the entire experimental period. The administration of cobalt significantly increased HIF-1α expression in the kidney. The increased expression of HIF-1α ameliorated CsA-induced afferent arteriolopathy and tubulointerstitial injury in the kidney. Cobalt significantly reduced the infiltration of macrophages/monocytes into the renal tubulointerstitium. In addition, HIF activation by cobalt reduced the number of CsA-induced apoptotic cells in the kidney. Subsequently, HK-2 human renal tubular epithelial cells were used for in vitro experiments. They were pre-treated with 150 µM of cobalt to activate HIF, and then exposed to 10 µM CsA. HIF activation by cobalt decreased the CsA-induced apop...Continue Reading

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Jun 20, 2014·International Journal of Molecular Sciences·Yan-Bo ZhangGuo Shao
Jul 3, 2013·Basic & Clinical Pharmacology & Toxicology·Jian-Pu ZhengWen Peng
Aug 27, 2013·Journal of Receptor and Signal Transduction Research·Song Mao, Songming Huang
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