Acute endotoxemia in mice induces downregulation of megalin and cubilin in the kidney
| Autor: | Frank Schweda, Andrea Schreiber, Franziska Theilig, Klaus Höcherl |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Time Factors 030232 urology & nephrology urologic and male genital diseases Kidney Concentrating Ability Kidney Tubules Proximal Rats Sprague-Dawley Mice 0302 clinical medicine Cells Cultured 0303 health sciences Kidney Mice Inbred BALB C biology Chemistry lipopolysaccharide Acute kidney injury Acute Kidney Injury Endocytosis Low Density Lipoprotein Receptor-Related Protein-2 medicine.anatomical_structure Nephrology Reperfusion Injury medicine.symptom Fluorescein-5-isothiocyanate medicine.medical_specialty Serum albumin Down-Regulation Receptors Cell Surface ischemia acute renal failure 03 medical and health sciences Renal tubular dysfunction Internal medicine medicine Albuminuria Animals RNA Messenger Serum Albumin albumin 030304 developmental biology Renal ischemia Albumin Cubilin medicine.disease Endotoxemia Rats Disease Models Animal Endocrinology inflammation biology.protein Biomarkers |
| Zdroj: | Kidney international |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2012.62 |
| Popis: | Severe sepsis is often accompanied by acute renal failure with renal tubular dysfunction. Albuminuria is a common finding in septic patients and we studied whether it was due to an impairment of proximal tubular endocytosis of filtered albumin. We studied the regulation of megalin and cubilin, the two critical multiligand receptors responsible for albumin absorption, during severe experimental endotoxemia. Lipopolysaccharide (LPS) caused a time- and dose-dependent suppression of megalin and cubilin expression that was paralleled by a decrease in plasma albumin levels and an increase in the urine concentration of albumin in mice. Incubation of rat renal cortical slices with LPS also reduced the mRNA expression of megalin and cubilin. Further, LPS suppressed megalin and cubilin mRNA expression in murine primary proximal tubule cells and decreased the uptake of FITC albumin in these cells. In addition, the increase in urine levels of albumin in response to ischemia/reperfusion-induced acute renal failure was paralleled by a decrease in the expression of megalin and cubilin. Thus, our data indicate that the expression of megalin and cubilin is decreased during experimental endotoxemia and in response to renal ischemia/reperfusion injury. This downregulation may contribute, in part, to an increase in urine levels of albumin during acute renal failure. |
| Databáze: | OpenAIRE |
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