ArticleAmerican journal of physiology. Renal physiology2012
Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response".
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- Alginate oligosaccharides attenuate obesity-associated kidney injury through modulation of the intestinal environment with renoprotection transferable by small intestinal contents.Frontiers in nutrition · 2026Article
- Haptoglobin as a novel predictor of visceral involvement and relapse in adult IgAV patients.Clinical rheumatology · 2025Article
- Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model.ACS pharmacology & translational science · 2024Article
- Differential renal proteomics analysis in a novel rat model of iodinated contrast-induced acute kidney injury.Renal failure · 2023Article
- IL-6 mediates the hepatic acute phase response after prerenal azotemia in a clinically defined murine model.American journal of physiology. Renal physiology · 2023Article
- A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells.International journal of molecular sciences · 2022Review
- Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases.International journal of molecular sciences · 2021Review
- Extensive Changes in Transcriptomic "Fingerprints" and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused byFrontiers in cellular and infection microbiology · 2020Article
- The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury.Frontiers in medicine · 2020Review
- The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice.International journal of molecular sciences · 2019Article
- Mechanisms of haemolysis-induced kidney injury.Nature reviews. Nephrology · 2019Review
- Rat models of colistin nephrotoxicity: previous experimental researches and future perspectives.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2019Review
- Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI.Journal of the American Society of Nephrology : JASN · 2018Article
- Genetic markers for urine haptoglobin is associated with decline in renal function in type 2 diabetes in East Asians.Scientific reports · 2018Article
- Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.Malaria journal · 2017Observational
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- Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure.Kidney international · 2016Article
- Marked protection against acute renal and hepatic injury after nitrited myoglobin + tin protoporphyrin administration.Translational research : the journal of laboratory and clinical medicine · 2015Article
- Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy.World journal of diabetes · 2015Article
- Acute hepatic ischemic-reperfusion injury induces a renal cortical "stress response," renal "cytoresistance," and an endotoxin hyperresponsive state.American journal of physiology. Renal physiology · 2014Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
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 observations that urine samples from 16 patients with established AKI had statistically higher (∼12×) urinary Hp levels than urine samples from either normal subjects or from 15 patients with chronic kidney disease. These AKI-associated urinary Hp increases mirrored those seen for urinary neutrophil gelatinase-associated lipoprotein, a well accepted AKI biomarker gene. In summary, these studies provide the first evidence that AKI evokes rapid, marked, and sustained induction of the proximal tubule Hp gene. Hp's known antioxidant, as well as its protean pro- and anti-inflammatory, actions imply potentially diverse effects on the evolution of acute tubular injury.
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