title: MMP9 limits apoptosis and stimulates branching morphogenesis during kidney development.
abstract: Early events in kidney organogenesis involve reciprocal interactions between the ureteric bud and the metanephric mesenchyme, which lead to remodeling of the extracellular matrix. This remodeling involves matrix metalloproteases (MMPs), but the specific roles of individual MMPs in kidney development are not completely understood. Here, we analyzed MMP9-deficient mice at the first step of kidney development and found that MMP9 deficiency delayed embryonic kidney maturation and increased apoptosis ex vivo by 2.5-fold. These early defects resulted in a 30% decrease in nephron number, a 20% decrease in adult kidney weight, and altered kidney function and morphology at 12 mo. The membrane form of stem cell factor (SCF) increased, whereas the activated form of the SCF receptor, c-kit, decreased in MMP9-deficient embryonic kidneys. In organotypic culture, MMP9-deficient kidneys failed to secrete SCF, and addition of recombinant SCF partially rescued both apoptosis and the branching defect. In conclusion, these data show that MMP9 protects mesenchymal cells from apoptosis during kidney development and stimulates ureteric bud branching morphogenesis, most likely by releasing the soluble form of SCF, suggesting that normal renal development requires MMP9.
authors.affiliation: Université Pierre et Marie Curie University of Paris 06, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnould
authors.forename: Martine
authors.initials: M
authors.lastname: Lelièvre-Pégorier
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lelongt
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D007668:Kidney / Q000196:embryology* / Q000473:pathology / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D011401:Promoter Regions, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019089:Stem Cell Factor / Q000032:analysis
chemical_list: D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020780:Matrix Metalloproteinase 9