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