Abstract
Background: The epidermal growth factor (EGF) system plays an important role in the development and function of the kidneys. Studies have suggested this system to protect against acute renal injury and to prevent the progression of chronic kidney disease. We have demonstrated that cobalamin (Cbl) modulates the expression of the EGF system in mouse spinal cord. Here, we explore the effects of Cbl treatment on the mouse kidney expression of members of the EGF system comparing these with the expression in the submaxillary gland and liver. Methods: Following four weeks of administrating different doses of Cbl, we analysed kidney, submaxillary gland, and liver mRNA levels of the four EGF system receptors and the activating ligands EGF and heparin-binding EGF-like growth factor using quantitative reverse transcription-PCR. In addition, we analysed mRNA expression of the renal tubular injury markers, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Results: In controls, kidney expression of EGF system receptors and ligands was similar to or more than twice the levels in the submaxillary gland. A relatively high expression of the EGF receptor was observed in liver tissue, but only low or no expression of other EGF related molecules. Treatment with Cbl decreased expression of the EGF system in the kidneys in a dose-dependent manner, while no or little change was observed in other organs. No alterations were observed in the markers of kidney tubular injury after Cbl administration. Conclusions: Our results show modulation of the renal EGF system expression in mice following long term Cbl administration. This may have implications for prevention of progressive kidney disease. In addition, differences in the expression of the EGF receptors and ligands in liver, submaxillary gland and kidney were demonstrated.
Highlights
The epidermal growth factor (EGF) system consists of four receptor tyrosine kinases (EGF receptor (EGFR), HER1, HER2, HER3 and HER4) and more than ten ligands including EGF and heparin-binding EGFlike growth factor (HB-EGF) [Melenhorst et al, 2008]
All analysed components of the EGF system showed a dose-dependent decline in the mRNA expression profiles; and for HER2, HB-EGF, and EGF, the decline was significantly greater in animals treated with very high- doses compared to high doses of Cbl
We show differential expression of the EGF system in mice kidney, submaxillary glands and liver, and that in the kidney, the mRNA levels of this system can be significantly decreased upon four weeks of treatment with very high or high doses of Cbl
Summary
The epidermal growth factor (EGF) system consists of four receptor tyrosine kinases (EGF receptor (EGFR), HER1, HER2, HER3 and HER4) and more than ten ligands including EGF and heparin-binding EGFlike growth factor (HB-EGF) [Melenhorst et al, 2008]. The epidermal growth factor (EGF) system plays an important role in the development and function of the kidneys. Studies have suggested this system to protect against acute renal injury and to prevent the progression of chronic kidney disease. Methods: Following four weeks of administrating different doses of Cbl, we analysed kidney, submaxillary gland, and liver mRNA levels of the four EGF system receptors and the activating ligands EGF and heparin-binding EGF-like growth factor using quantitative reverse transcription-PCR. Conclusions: Our results show modulation of the renal EGF system expression in mice following long term Cbl administration This may have implications for prevention of progressive kidney disease. Differences in the expression of the EGF receptors and ligands in liver, submaxillary gland and kidney were demonstrated
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