A Causative Role of Stromelysin-3 in Extracellular Matrix Remodeling and Epithelial Apoptosis during Intestinal Metamorphosis in Xenopus laevis

Atsuko Ishizuya-Oka,Daniel R. Buchholz,Yun-Bo Shi,Liezhen Fu,Hiroki Matsuda,Tosikazu Amano

doi:10.1074/jbc.m413275200

Abstract

The matrix metalloproteinases are a family of proteases capable of degrading various components of the extracellular matrix. Expression studies have implicated the involvement of the matrix metalloproteinase stromelysin-3 (ST3) in tissue remodeling and pathogenesis. However, the in vivo role of ST3 has been difficult to study because of a lack of good animal models. Here we used intestinal remodeling during thyroid hormone-dependent metamorphosis of Xenopus laevis as a model to investigate in vivo the role of ST3 during postembryonic organ development in vertebrates. We generated transgenic tadpoles expressing ST3 under control of a heat shock-inducible promoter. We showed for the first time in vivo that wild type ST3 but not a catalytically inactive mutant was sufficient to induce larval epithelial cell death and fibroblast activation, events that normally occur only in the presence of thyroid hormone. We further demonstrated that these changes in cell fate are associated with altered gene expression in the intestine and remodeling of the intestinal basal lamina. These results thus suggest that ST3 regulates cell fate and tissue morphogenesis through direct or indirect ECM remodeling.

Highlights

A Causative Role of Stromelysin-3 in Extracellular Matrix Remodeling and Epithelial Apoptosis during Intestinal Metamorphosis in Xenopus laevis*
The primer/probe set for the endogenous ST3 had the forward primer located in the 5Ј-untranslated region; the primer/probe set for the transgenic ST3 fused to green fluorescent protein (GFP) (ST3-GFP) had the reverse primer in the GFP region; the primer/probe set for both the endogenous ST3 and transgenic ST3-GFP had the primers and probes all in the ST3 coding region
The first is the development of the tadpole intestine during embryogenesis, leading to the formation of simple tubular organ consisting of predominantly a single layer of tadpole/larval epithelial cells surrounded by thin layers of connective tissue and muscles

Summary

Introduction

A Causative Role of Stromelysin-3 in Extracellular Matrix Remodeling and Epithelial Apoptosis during Intestinal Metamorphosis in Xenopus laevis*. We used intestinal remodeling during thyroid hormone-dependent metamorphosis of Xenopus laevis as a model to investigate in vivo the role of ST3 during postembryonic organ development in vertebrates. We further demonstrated that these changes in cell fate are associated with altered gene expression in the intestine and remodeling of the intestinal basal lamina These results suggest that ST3 regulates cell fate and tissue morphogenesis through direct or indirect ECM remodeling. The matrix metalloproteinases (MMPs) are a superfamily of matrix-degrading proteases, including collagenases, gelatinases, stromelysins, and membrane type MMPs [1,2,3]. They are either secreted extracellularly or bound to plasma membrane. It serves as the structural scaffold to hold cells together in various organs or tissues

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Results

Conclusion