Journal of Pharmacological Sciences | |
Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury:The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis | |
Tomoaki Iwai1  Tatsuya Nakatani1  Nobuyuki Kuwabara1  Katsuyuki Miura3  Toshihiro Asai1  Satoshi Tamada1  Tokihito Yukimura3  Kae Teramoto3  Junji Uchida1  Noriko Kaneda3  Toshiyuki Komiya2  | |
[1] Department of Urology, Osaka City University Medical School, Japan;Department of Medicine, The Tazuke Kofukai, Medical Research Institute, Kitano Hospital, Japan;Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School, Japan | |
关键词: nuclear factor κB; renal fibrosis; nephrotoxicity; unilateral ureteral obstruction; oral adsorbent; | |
DOI : 10.1254/jphs.FMJ05003X4 | |
学科分类:药学 | |
来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society | |
【 摘 要 】
References(21)Cited-By(18)Tubulointerstitial fibrosis is a common feature of many progressive renal diseases and is a main determinant that leads to an irreversible loss of renal function. In chronic cyclosporin A nephrotoxicity, we previously reported that inflammatory responses such as macrophage infiltration preceded interstitial fibrosis. This inflammation was accompanied by an elevation in renal nuclear factor κB (NF-κB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-κB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin®) significantly attenuated the increase in renal NF-κB activity and concomitantly reduced interstitial inflammation and renal fibrosis in chronic renal failure rats. Elimination of indoxyl sulfate by this adsorbent is likely involved in this mechanism since it is known that indoxyl sulfate activates NF-κB in renal tubular cells. It is suggested that strategy aiming at NF-κB inhibition is important to prevent the progression of renal fibrosis.
【 授权许可】
Unknown
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