October 12, 2018

Targeting diabetic kidney disease

Pathways activated by the epidermal growth factor receptor may be attractive targets to treat diabetic kidney disease, according to new findings from Vanderbilt investigators.

Diabetic nephropathy (DN) is a kidney disease characterized by loss of kidney function in patients with diabetes.

Raymond Harris, MD, and colleagues previously showed that the epidermal growth factor receptor (EGFR) is activated in mouse models of type 1 diabetes, and that drugs which inhibit EGFR prevent the development of DN.

EGFR becomes active when phosphate molecules attach at specific tyrosine sites in the protein. The phosphorylated tyrosines become the docking sites for a variety of molecules that regulate cell proliferation, maturation and cell death.

Now in a study published in the journal Diabetes, Harris, Ming-Zhi Zhang, MD, and colleagues show that blocking EGFR tyrosine kinase activity with the drug erlotinib not only slowed the progression of DN but also improved weight gain and reduced insulin resistance in mice. Their work suggests that pathways activated by EGFR may be attractive targets to treat DN.

For his discovery of EGF, Vanderbilt’s Stanley Cohen, PhD, shared the Nobel Prize in medicine in 1986.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants DK051265, DK062794, DK095785, DK114809) and by the U.S. Department of Veterans Affairs.