Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury.

Chen J, Chen JK, Harris RC
Kidney Int. 2012 82 (1): 45-52

PMID: 22418982 · PMCID: PMC3376190 · DOI:10.1038/ki.2012.43

To determine the role of epidermal growth factor receptor (EGFR) activation in renal functional and structural recovery from acute kidney injury (AKI), we generated mice with a specific EGFR deletion in the renal proximal tubule (EGFR(ptKO)). Ischemia-reperfusion injury markedly activated EGFR in control littermate mice; however, this was inhibited in either the knockout or wild-type mice given erlotinib, a specific EGFR tyrosine kinase inhibitor. Blood urea nitrogen and serum creatinine increased to a comparable level in EGFR(ptKO) and control mice 24 h after reperfusion, but the subsequent rate of renal function recovery was markedly slowed in the knockout mice. Twenty-four hours after reperfusion, both the knockout and the inhibitor-treated mice had a similar degree of histologic renal injury as control mice, but at day 6 there was minimal evidence of injury in the control mice while both EGFR(ptKO) and erlotinib-treated mice still had persistent proximal tubule dilation, epithelial simplification, and cast formation. Additionally, renal cell proliferation was delayed due to decreased ERK and Akt signaling. Thus, our studies provide both genetic and pharmacologic evidence that proximal tubule EGFR activation plays an important role in the recovery phase after acute kidney injury.

MeSH Terms (23)

Acute Kidney Injury Animals Biomarkers Blood Urea Nitrogen Creatinine Disease Models, Animal Enzyme Activation ErbB Receptors Erlotinib Hydrochloride Extracellular Signal-Regulated MAP Kinases Gene Deletion Kidney Tubules, Proximal Mice Mice, Inbred BALB C Mice, Knockout Phosphatidylinositol 3-Kinase Phosphorylation Protein Kinase Inhibitors Proto-Oncogene Proteins c-akt Quinazolines Recovery of Function Reperfusion Injury Time Factors

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