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EGF Receptor Activation Stimulates SOX9 Expression in Injured Renal Proximal Tubule Epithelial Cells
Jianchun Chen1,2,3, Fenfen Peng2,3, Mengdi Jiang2,3
1Department of Veterans Affairs, Vanderbilt University Medical Center, Nashville, Tennessee.
Journal of the American Society of Nephrology : JASN
|September 2, 2025
Summary
Epidermal growth factor receptor (EGFR) activation is essential for SOX9 induction in kidney proximal tubule cells after acute kidney injury (AKI). This mechanism is key to understanding kidney repair and chronic kidney disease (CKD) development.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- SOX9 expression in renal proximal tubule cells (RPTCs) is vital for kidney repair post-acute kidney injury (AKI).
- Persistent SOX9 upregulation in RPTCs is linked to chronic kidney disease (CKD) development.
- Mechanisms of SOX9 induction by kidney injury require further elucidation.
Purpose of the Study:
- To investigate the role of epidermal growth factor receptor (EGFR) activation in regulating SOX9 expression in injured RPTCs.
- To elucidate the molecular pathways linking EGFR activation to SOX9 induction in the context of kidney injury.
Main Methods:
- Examined SOX9 and EGFR expression in human renal tubular epithelial cells from patients with acute tubular injury and chronic allograft nephropathy.
- Utilized mouse models, including EGFR tyrosine kinase-deficient mice, to study EGFR's role in SOX9 upregulation.
- Investigated the mechanism in cultured human RPTCs to confirm EGFR's effect on SOX9.
Main Results:
- Elevated and colocalized SOX9 and EGFR expression observed in human renal tubular epithelial cells.
- Overexpression of hHB-EGF in RPTCs increased SOX9, an effect abolished in EGFR-deficient mice.
- EGFR inhibition (genetic or pharmacologic) decreased SOX9 expression following ischemic AKI.
- Ischemic AKI activates proximal tubule EGFR, initiating the Akt-YAP/TAZ-TEAD pathway and SOX9 induction.
Conclusions:
- EGFR activation is a critical regulator of SOX9 expression in RPTCs following AKI.
- The EGFR-Akt-YAP/TAZ-TEAD signaling axis mediates SOX9 induction in response to kidney injury.
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