Lack of HB-EGF Expression is Protective against Chronic Kidney Disease under Diabetic Conditions

Chronic kidney disease affects about 1 out of 3 adults with diabetes that may result in kidney failure and possibly end-stage renal disease. The aim of this study is to determine the role of HB-EGF as a contributing factor to chronic kidney disease in streptozotocin induced diabetic mice. We find that streptozotocin-induced diabetic wild-type, human HB-EGF transgenic, HB-EGF heterozygous, and HB-EGF null mice resulted in hyperglycemic conditions compared to control mice, exhibited enlarged kidney size, weight, and glomerular cross-sectional area and were directly correlated to the levels of HB-EGF. Collagen formation was was observed in the kidneys of wild type, heterozygous, and transgenic streptozotocin-mice but absent in HB-EGF -/- as well as control mice suggesting that HB-EGF stimulates fibrosis. Serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels in streptozotocin-diabetic HB-EGF transgenic were significantly higher indicating HB-EGF may be contributing to chronic kidney disease. Collectively, these findings suggest that the lack of HB-EGF may be protective against steptozotocin-induced chronic kidney disease.