A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue
Autor: | Tae-Hwa Chun, Kevin B. Hotary, Farideh Sabeh, Alan R. Saltiel, Edward D. Allen, Stephen J. Weiss |
---|---|
Rok vydání: | 2006 |
Předmět: |
medicine.medical_specialty
Matrix Metalloproteinases Membrane-Associated Adipose tissue White adipose tissue Cell Enlargement Biology Carbohydrate metabolism Matrix metalloproteinase General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Adipocytes Matrix Metalloproteinase 14 medicine Animals Collagenases Fatty acid synthesis 030304 developmental biology Mice Knockout 0303 health sciences Adipogenesis Extramural Biochemistry Genetics and Molecular Biology(all) Stem Cells Cell Differentiation Hypertrophy Matrix Metalloproteinases Extracellular Matrix Cell biology Endocrinology Adipose Tissue Animals Newborn chemistry 030220 oncology & carcinogenesis Collagenase Collagen Membrane-Type Matrix Metalloproteinase psychological phenomena and processes medicine.drug |
Zdroj: | Cell. 125(3):577-591 |
ISSN: | 0092-8674 |
DOI: | 10.1016/j.cell.2006.02.050 |
Popis: | SummaryWhite adipose tissue (WAT) serves as the primary energy depot in the body by storing fat. During development, fat cell precursors (i.e., preadipocytes) undergo a hypertrophic response as they mature into lipid-laden adipocytes. However, the mechanisms that regulate adipocyte size and mass remain undefined. Herein, we demonstrate that the membrane-anchored metalloproteinase, MT1-MMP, coordinates adipocyte differentiation in vivo. In the absence of the protease, WAT development is aborted, leaving tissues populated by mini-adipocytes which render null mice lipodystrophic. While MT1-MMP preadipocytes display a cell autonomous defect in vivo, null progenitors retain the ability to differentiate into functional adipocytes during 2-dimensional (2-D) culture. By contrast, within the context of the 3-dimensional (3-D) ECM, normal adipocyte maturation requires a burst in MT1-MMP-mediated proteolysis that modulates pericellular collagen rigidity in a fashion that controls adipogenesis. Hence, MT1-MMP acts as a 3-D-specific adipogenic factor that directs the dynamic adipocyte-ECM interactions critical to WAT development. |
Databáze: | OpenAIRE |
Externí odkaz: |