Regulation of extracellular matrix remodeling and cell fate determination by matrix metalloproteinase stromelysin-3 during thyroid hormone-dependent post-embryonic development.
Interactions between cells and extracellular matrix (ECM), in particular the basement membrane (BM), are fundamentally important for the regulation of a wide variety of physiological and pathological processes. Matrix metalloproteinases (MMP) play critical roles in ECM remodeling and/or regulation of cell-ECM interactions because of their ability to cleave protein components of the ECM. Of particular interest among MMP is stromelysin-3 (ST3), which was first isolated from a human breast cancer and also shown to be correlated with apoptosis during development and invasion of tumor cells in mammals. We have been using intestinal remodeling during thyroid hormone (TH)-dependent amphibian metamorphosis as a model to study the role of ST3 during post-embryonic tissue remodeling and organ development in vertebrates. This process involves complete degeneration of the tadpole or larval epithelium through apoptosis and de novo development of the adult epithelium. Here, we will first summarize expression studies by us and others showing a tight spatial and temporal correlation of the expression of ST3 mRNA and protein with larval cell death and adult tissue development. We will then review in vitro and in vivo data supporting a critical role of ST3 in TH-induced larval epithelial cell death and ECM remodeling. We will further discuss the potential mechanisms of ST3 function during metamorphosis and its broader implications.
Shi
Yun-Bo
YB
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, MD 20892, USA. shi@helix.nih.gov
Fu
Liezhen
L
Hasebe
Takashi
T
Ishizuya-Oka
Atsuko
A
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000502:physiology*; D008675:Metamorphosis, Biological; D013963:Thyroid Hormones / Q000502:physiology*; D014982:Xenopus laevis
D013963:Thyroid Hormones; D053507:Matrix Metalloproteinase 11