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TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling
Carolin Lepa1, Sascha Hoppe1, Antje Stöber1
1Medizinische Klinik D, University Hospital Münster, Münster, Germany.
Journal of the American Society of Nephrology : JASN
|December 31, 2020
Summary
Neurotrophic tyrosine kinase receptor 3 (TrkC) is crucial for maintaining kidney podocyte health and glomerular integrity. Its dysregulation contributes to kidney disease by impacting insulin-like growth factor signaling.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Podocyte injury is a primary driver of chronic kidney disease, yet targeted therapies remain limited.
- Identifying novel signaling pathways involved in glomerular disease pathogenesis is critical.
- Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and influences their actin cytoskeleton.
Purpose of the Study:
- To investigate the role of TrkC in kidney podocyte development and maintenance.
- To explore the signaling pathways modulated by TrkC in the glomerulus.
Main Methods:
- Generation of nephron-specific TrkC knockout (TrkC-KO) and TrkC-overexpressing (TrkC-OE) mouse models.
- Analysis of glomerular structure, function, and protein signaling in TrkC-manipulated mice.
- Examination of TrkC expression in human diabetic kidney disease tissue.
Main Results:
- Both TrkC-KO and TrkC-OE mice exhibited age-dependent glomerular abnormalities, including enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, and podocyte loss, indicative of focal segmental glomerulosclerosis (FSGS).
- TrkC signaling influences the insulin-like growth factor 1 receptor (Igf1R) pathway in podocytes, with altered Igf1R phosphorylation observed in TrkC-manipulated kidneys.
- Elevated TrkC expression was detected in human diabetic kidney disease glomeruli.
Conclusions:
- TrkC is essential for maintaining glomerular integrity and podocyte health.
- TrkC signaling modulates Igf-related pathways within podocytes, highlighting its potential as a therapeutic target for kidney diseases.
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