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Extracellular matrix modulates mesangial cell apoptosis and mRNA expression of cathepsin-B and tissue
P C Singhal1, N Franki, S Kumari
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Abstract:
Mesangial matrix is a dynamic structure which modulates mesangial cell function. Since accumulation of matrix precedes the development of focal glomerulosclerosis, we studied the effect of different matrices on mesangial cell (MC) apoptosis. Suspended mesangial cells became apoptotic in a time dependent manner. Collagen type III did not modulate MC apoptosis when compared to cells grown on plastic. MCs grown on Matrigel, collagen type I and IV showed an increased number of apoptotic cells when compared to MCs grown on plastic. DNA end-labeling further confirmed these observations. MCs grown on Matrigel showed enhanced (P < 0.05) mRNA expression for tissue transglutaminase (TTG) and cathepsin-B. Mesangial cells grown on Matrigel also showed enhanced expression of superoxide dismutase (SOD). We conclude that mesangial cells require attachment to the matrix for their survival and alteration of the quality of matrix modulates mesangial cell apoptosis.
Insights
Mesangial cells undergo apoptosis when detached. Different matrices, like Matrigel and collagen types I and IV, influence mesangial cell (MC) apoptosis and gene expression, impacting kidney disease development.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Mesangial matrix is crucial for mesangial cell (MC) function and its accumulation precedes focal glomerulosclerosis.
- Understanding the role of extracellular matrix in MC apoptosis is vital for kidney disease research.
Purpose of the Study:
- To investigate the impact of various matrices on mesangial cell (MC) apoptosis.
- To explore how matrix composition influences MC survival and gene expression.
Main Methods:
- Cultured suspended mesangial cells (MCs) on different matrices (plastic, collagen types I, III, IV, and Matrigel).
- Assessed MC apoptosis using DNA end-labeling.
- Quantified mRNA expression of tissue transglutaminase (TTG), cathepsin-B, and superoxide dismutase (SOD) in MCs.
Main Results:
- Suspended MCs exhibited time-dependent apoptosis.
- Collagen type III did not affect MC apoptosis compared to plastic.
- Matrigel, collagen type I, and IV significantly increased MC apoptosis.
- MCs on Matrigel showed enhanced mRNA expression for TTG, cathepsin-B, and SOD.
Conclusions:
- Mesangial cell (MC) survival is dependent on matrix attachment.
- Altering matrix composition significantly modulates MC apoptosis and gene expression.
- These findings offer insights into the pathogenesis of kidney diseases like focal glomerulosclerosis.