Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response".

American Journal of Physiology. Renal Physiology
R A ZagerAli C M Johnson

Abstract

Haptoglobin (Hp) synthesis occurs almost exclusively in liver, and it is rapidly upregulated in response to stress. Because many of the pathways that initiate hepatic Hp synthesis are also operative during acute kidney injury (AKI), we tested whether AKI activates the renal cortical Hp gene. CD-1 mice were subjected to six diverse AKI models: ischemia-reperfusion, glycerol injection, cisplatin nephrotoxicity, myoglobinuria, endotoxemia, and bilateral ureteral obstruction. Renal cortical Hp gene induction was determined either 4-72 h or 1-3 wk later by measuring Hp mRNA and protein levels. Relative renal vs. hepatic Hp gene induction during endotoxemia was also assessed. Each form of AKI induced striking and sustained Hp mRNA increases, leading to ∼10- to 100-fold renal Hp protein elevations (ELISA; Western blot). Immunohistochemistry, and isolated proximal tubule assessments, indicated that the proximal tubule was the dominant (if not only) site of the renal Hp increases. Corresponding urinary and plasma Hp elevations were surrogate markers of this response. Endotoxemia evoked 25-fold greater Hp mRNA increases in kidney vs. liver, indicating marked renal Hp gene reactivity. Clinical relevance of these findings was suggested by ...Continue Reading

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Sep 21, 2012·American Journal of Physiology. Renal Physiology·Qingqing Wei, Zheng Dong
Sep 21, 2012·American Journal of Physiology. Renal Physiology·Richard A ZagerKirsten Becker
Dec 1, 2012·American Journal of Physiology. Renal Physiology·Karl A NathZvonimir S Katusic
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May 14, 2016·American Journal of Physiology. Renal Physiology·Richard A ZagerKirsten Frostad
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Jan 6, 2021·Diabetes/metabolism Research and Reviews·Xiao-Min ZhengJin-Kui Yang
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