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IGF-1-induced lipid accumulation impairs mesangial cell migration and contractile function
Anne K Berfield1, Dennis L Andress, Christine K Abrass
1Division of Nephrology, Department of Medicine, Veteran Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA.
Kidney International
|September 18, 2002
Summary
Insulin-like growth factor-1 (IGF-1) causes lipid accumulation in mesangial cells, impairing their migration and contraction. Removing lipids restores normal cell function, offering insights into kidney diseases.
Area of Science:
- Nephrology
- Cell Biology
- Endocrinology
Background:
- Chronic exposure to insulin-like growth factor-1 (IGF-1) induces lipid accumulation in mesangial cells.
- These lipid-laden mesangial cells exhibit characteristics of foam cells, suggesting potential functional alterations.
Purpose of the Study:
- To investigate the functional consequences of IGF-1-induced lipid accumulation in mesangial cells.
- To determine if lipid accumulation affects mesangial cell migration in response to IGF-binding protein-5 (IGFBP-5) and contractility to angiotensin II (Ang II).
Main Methods:
- Lipid-laden mesangial cells were assessed for migratory response to IGFBP-5 and contractile response to Ang II.
- IGFBP-5 binding and signal transduction pathways for migration were examined.
- Lipid removal from cells was performed to confirm the role of lipid accumulation in impaired contractility.
Main Results:
- Lipid-laden mesangial cells demonstrated impaired migration in response to IGFBP-5, despite normal IGFBP-5 binding.
- IGFBP-5 failed to activate cdc42, a key GTPase for migration, in lipid-laden cells, indicating a signal transduction defect.
- Mesangial cells treated with IGF-1 showed reduced contraction to Ang II; this effect was reversible upon lipid removal.
Conclusions:
- IGF-1-induced lipid accumulation in mesangial cells significantly impairs their migratory and contractile functions.
- These findings are crucial for understanding the pathophysiology of kidney diseases characterized by mesangial foam cells, including diabetic nephropathy and focal segmental glomerulosclerosis.