Increased epidermal growth factor in experimental diabetes related kidney growth in rats

Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease

“…In one study [167] a pronounced increase in diurnal urine EGF excretion was seen but no statistically significant change in renal EGF within the first 7 days after induction of diabetes. These findings were confirmed in a recent study [168] where unchanged concentrations of kidney and plasma EGF were reported, within the first week after induction of diabetes, along with a threefold increase in urinary EGF excretion. In addition, renal EGF mRNA as measured both by northern blotting and in situ hybridization, was increased by 4±8 times [168,169].…”

“…These findings were confirmed in a recent study [168] where unchanged concentrations of kidney and plasma EGF were reported, within the first week after induction of diabetes, along with a threefold increase in urinary EGF excretion. In addition, renal EGF mRNA as measured both by northern blotting and in situ hybridization, was increased by 4±8 times [168,169]. After a diabetes duration of 2±3 weeks the urinary EGF excretion was restored to normal or even tended to reach subnormal levels compared with non-diabetic animals [169,170].…”

Collagen I induction by high glucose levels is mediated by epidermal growth factor receptor and phosphoinositide 3-kinase/Akt signalling in mesangial cells

“…Indeed, we found the EGFR to be activated by high glucose levels and this transactivation was shown to be required for downstream Akt activation and collagen I synthesis in mesangial cells by use of both a specific tyrphostin inhibitor and a dominant-negative construct. Interestingly, EGF upregulation has been observed in the streptozotocin diabetes model, with increased EGF transcript upregulation and urinary excretion as early as 1 day after streptozotocin injection [42]. Although expression has been noted only in tubular segments, EGFR inhibition was able to reduce glomerular hypertrophy after 3 weeks of streptozotocin-induced diabetes [43].…”

Effect of Protein Kinase Cβ Inhibition on Renal Hemodynamic Function and Urinary Biomarkers in Humans With Type 1 Diabetes: A Pilot Study

“…PKC␤ activation in diabetes is associated with loss of key protective trophic factors, such as epidermal growth factor (EGF) (3), and with expression of proinflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1) (4,5). Much less is known about the role of PKC␤ activation in the pathogenesis of renal hemodynamic and molecular abnormalities in human diabetes.…”