Table 3.
Kidney epidermal growth factor receptor pathophysiology
| Model | Intervention | Outcome and intermediate | Reference |
|---|---|---|---|
| Acute kidney injury (mercuric chloride injection) | Waved-2 mice | Resulted in slower recovery from acute renal injury; associated with reduced EGFR activation and DNA synthesis | 150 |
| Acute kidney injury (ischemia/reperfusion) | Proximal tubule EGFR KO mice or erlotinib | Resulted in slower recovery from acute renal injury; associated with reduced ERK and Akt activation | 151 |
| Acute glomerulonephritis (anti-GBM injection) | Podocyte EGFR KO mice or AG1478 | Prevented renal dysfunction, pathology, and inflammation | 153 |
| Hypertensive renal damage (L-NAME infusion) | Gefitinib | Reduced glomerular matrix deposition, ERK activation, and renal dysfunction | 154 |
| Hypertensive renal damage (L-NAME infusion) | Gefitinib upon renal damage | Resulted in nonreversible renal pathology and hypertension, but normalized renal blood flow and endothelial function | 122 |
| Hypertensive renal damage (AngII infusion) | Proximal tubule dnEGFR transgenic | Prevented renal dysfunction and fibrosis; ADAM17 and TGF-α are pivotal components to the EGFR activation | 155 |
| Hypertensive renal fibrosis (AngII infusion) | Proximal tubule EGFR KO mice or erlotinib | Prevented renal fibrosis; the downstream signal of EGFR includes ERK, TGF-β, and SMAD2/3 | 62 |
| Hypertensive renal fibrosis (ISO infusion) | Gefitinib | Reduced hypertrophy and apoptosis; altered βAR-sensitive cytokines including CCL2 and TNF-α | 89 |
| Renal fibrosis (ischemic reperfusion) | Waved-2 mice | Enhanced acute renal damage, but resulted in development of less fibrosis and activated Akt/STAT3 at later stage | 152 |
| Diabetic nephropathy (STZ treatment) | PKI-166 | Reduced kidney enlargement and epithelial cell proliferation, but did not affect hyperfiltration | 157 |
| Diabetic nephropathy (STZ treatment) | eNOS KO mice with erlotinib treatment | Reduced diabetic nephropathy, ER stress, CTGF and collagen; increased AMPK activation and autophagy | 158 |
| Diabetic nephropathy (STZ treatment) | Podocyte EGFR KO mice | Reduced podocyte loss, TGF-β, and mitochondrial ROS; decreased caspase 3 cleavage and restored BCL2 | 159 |
| Chronic renal failure (5/6 nephrectomy) | PKI-166 | Did not prevent renal damage and dysfunction, but attenuated hypertension | 59 |
| Chronic renal failure (3/4 nephrectomy) | Proximal tubule dnEGFR transgenic | Reduced proximal tubule lesions | 160 |
| Chronic renal failure (unilateral ureteral obstruction) | Waved-2 or gefitinib | Reduced renal fibrosis; attenuated expression of TGF-β1 and activation of Smad3, STAT3, and ERK | 161 |
| Polycystic kidney (BPK mice) | EKI-785 | Reduced cystic lesions, improved renal function, and increased life span | 162 |
Abbreviations: ADAM, a disintegrin and metalloprotease; AMPK, AMP-activated protein kinase; AngII, angiotensin II; BCL2, B-cell lymphoma 2; βAR, β-adrenergic receptor; BPK, polycystic kidney mutation of BALB/c origin; CCL2, chemokine C-C motif ligand 2; CTGF, connective tissue growth factor; dnEGFR, dominant-negative EGFR; EGFR, epidermal growth factor receptor; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; GBM, glomerular basement membrane; ISO, isoproterenol; KO, knockout; ROS, reactive oxygen species; SMAD2/3, mothers against decapentaplegic homolog 2/3; STAT3, signal transducer and activator of transcription 3; STZ, streptozotocin; TGF, transforming growth factor; TNF-α/β, tumor necrosis factor alpha/beta.