Epidermal Growth Factor Signaling in Kidney Pathologies

Epidermal Growth Factor (EGF) signalling plays a central role in renal development, homeostasis and repair, yet its dysregulation contributes to a spectrum of kidney pathologies. Binding of EGF and related ligands to the Epidermal Growth Factor Receptor (EGFR) activates intracellular cascades including the MAPK/ERK, PI3K/AKT and JAK/STAT pathways. In acute injury, EGFR activation promotes epithelial proliferation and restitution of tubular integrity. However, sustained or aberrant signalling drives interstitial fibrosis, glomerulosclerosis, inflammation and podocyte injury. Transactivation of EGFR by angiotensin II, transforming growth factor-β and reactive oxygen species further amplifies pro-fibrotic and pro-inflammatory programmes. Enhanced EGFR expression in pericytes and fibroblasts stimulates their migration and proliferation, seeding the myofibroblast pool that lays down excess extracellular matrix. In glomerular disease, EGFR-mediated podocyte dysfunction and impaired autophagy accelerate proteinuria and decline in filtration. The global burden of chronic kidney disease and limited treatment options have spurred efforts to repurpose EGFR inhibitors and to identify complementary strategies—such as modulating counter-regulatory axes of the renin-angiotensin-aldosterone system—to restore signalling balance. Recent advances have begun to unravel cell-type specificity and temporal dynamics of EGFR activation, offering new avenues for targeted intervention in diabetic nephropathy, hypertensive nephropathy, fibrotic kidney disease and acute tubular injury.

Research from Nature Portfolio

Recent studies have demonstrated that EGFR expression is markedly increased in interstitial fibroblasts and pericytes in human and experimental models of renal fibrosis. Selective deletion of EGFR in the fibroblast/pericyte lineage attenuates matrix deposition and tissue scarring in models of ureteral obstruction, ischaemia–reperfusion and toxin-induced injury. Mechanistic investigations using single-cell and single-nucleus transcriptomics reveal that EGFR does not directly drive myofibroblast differentiation but is essential for the early migratory and proliferative phases of pericyte activation, priming these cells for subsequent transformation under the influence of profibrotic cytokines. These findings position EGFR as a nodal regulator of the fibrosis cascade and highlight its potential as a therapeutic target to prevent progression to end-stage renal disease.

Epidermal Growth Factor Signaling in Kidney Pathologies publication trend

The graph below shows the total number of articles in epidermal growth factor signaling in kidney pathologies across all publications each year (not limited to Nature Index journals).

Technical terms

Epidermal Growth Factor Receptor (EGFR): A membrane-bound tyrosine kinase that, upon binding of EGF family ligands, initiates intracellular signalling cascades governing cell proliferation, survival and migration.

Pericyte: A specialised perivascular cell that, when activated by injury signals, can migrate into the interstitium and contribute to the myofibroblast pool driving fibrosis.

Myofibroblast: A contractile, α-smooth muscle actin–expressing cell responsible for extracellular matrix deposition during fibrotic remodelling.

Podocyte Autophagy: A lysosome-mediated degradation process in glomerular epithelial cells that maintains podocyte health and filtration barrier integrity.

Transactivation: Indirect activation of a receptor (such as EGFR) by non-canonical stimuli (for example angiotensin II or reactive oxygen species) without direct ligand binding.

References

1. Epidermal growth factor receptor activation is essential for kidney fibrosis development. Nature Communications (2023).
2. “Qi Nan” agarwood restores podocyte autophagy in diabetic kidney disease by targeting EGFR signaling pathway. Chinese Medicine (2024).
3. Targeting the epidermal growth factor receptor (EGFR/ErbB) for the potential treatment of renal pathologies. Frontiers in Pharmacology (2024).