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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
MMP9 limits apoptosis and stimulates branching morphogenesis during kidney development
Catherine Arnould1, Martine Lelièvre-Pégorier, Pierre Ronco
1Université Pierre et Marie Curie University of Paris 06, Paris, France.
Journal of the American Society of Nephrology : JASN
|August 29, 2009
Summary
Matrix metalloprotease-9 (MMP9) is crucial for kidney development. MMP9 deficiency impairs embryonic kidney maturation, reduces nephron number, and affects adult kidney function, highlighting MMP9
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- Kidney organogenesis relies on ureteric bud and metanephric mesenchyme interactions.
- Extracellular matrix remodeling, involving matrix metalloproteases (MMPs), is critical but poorly understood.
- Specific roles of individual MMPs in renal development require further investigation.
Purpose of the Study:
- To investigate the role of matrix metalloprotease-9 (MMP9) in early kidney organogenesis.
- To determine the impact of MMP9 deficiency on embryonic kidney development and maturation.
- To elucidate the mechanisms by which MMP9 influences renal development.
Main Methods:
- Analysis of MMP9-deficient mice during early kidney development.
- Ex vivo apoptosis assays.
- Organotypic kidney culture.
- Measurement of nephron number, kidney weight, and kidney function.
- Analysis of stem cell factor (SCF) and c-kit expression.
Main Results:
- MMP9 deficiency delayed embryonic kidney maturation and increased apoptosis by 2.5-fold.
- Reduced nephron number (30%) and adult kidney weight (20%) were observed in MMP9-deficient mice.
- MMP9 deficiency altered kidney function and morphology, decreased SCF secretion, and reduced c-kit activation.
Conclusions:
- MMP9 protects metanephric mesenchymal cells from apoptosis during kidney development.
- MMP9 stimulates ureteric bud branching morphogenesis, likely via releasing soluble stem cell factor (SCF).
- Normal renal development is dependent on the function of MMP9.
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