The Epidermal Growth Factor Receptor: A Potential Therapeutic Target in Chronic Kidney Disease
Chronic kidney disease is a clinical syndrome characterized by a gradual loss
of kidney function that persists for >3 months with health implications and affects nearly 500
million people worldwide.
Diabetes and hypertension are the 2 most common causes of CKD,
which account for up to two-thirds of the cases.
Accumulating evidence has shown that hyperuricemia is tightly associated
with the pathogenesis of CKD.
Prior studies demonstrate that decreasing uric acid levels delays the development of
CKD and slows its progression and uric acid is an independent predictor of future development
of CKD.
The mechanistic processes by which hyperuricemia induces chronic renal injury
involve deposition of uric acid crystals in the collecting duct of the kidney, renal angiotensin
system activation, oxidative stress, tubular epithelial cell transition and inflammation.
Upon activation, EGFR undergoes dimerization, a transition from an inactive monomeric form to an active homodimer. EGFR dimerization promotes its intrinsic intracellular protein-tyrosine kinase
activity, which results in autophosphorylation of several tyrosine residues in the C-terminal
domain of EGFR.
This autophosphorylation initiates several signal transduction cascades such
as the mitogen-activated protein kinases, protein kinase B also known as Akt
and Jun amino-terminal kinases pathways, regulating cell migration, adhesion, and proliferation.
Numerous studies have shown that EGFR activation contributes to chronic renal injury
and glomerular sclerosis.
Intriguingly, a recent study by Liu et al4 reported that EGFR activation
was critically involved in uric acid-induced chronic renal injury
in a rat model of Hyperuricemic nephropathy.
Mechanistically, inhibition of EGFR abrogated the expression of
TGF-β and phosphorylation of Smad3,
and blocked NF-kB pathway activation and macrophage infiltration in the kidney of Hyperuricemic rat.
Nephrol Open J. 2016; 3(1): e1-e2. doi: 10.17140/NPOJ-3-e006
