Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
PLoS One
2007 Oct 03;210:e1000. doi: 10.1371/journal.pone.0001000.
Show Gene links
Show Anatomy links
Membrane type-1 matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 RNA levels mimic each other during Xenopus laevis metamorphosis.
Walsh LA
,
Carere DA
,
Cooper CA
,
Damjanovski S
.
???displayArticle.abstract???
Matrix metalloproteinases (MMPs) and their endogenous inhibitors TIMPs (tissue inhibitors of MMPs), are two protein families that work together to remodel the extracellular matrix (ECM). TIMPs serve not only to inhibit MMP activity, but also aid in the activation of MMPs that are secreted as inactive zymogens. Xenopus laevis metamorphosis is an ideal model for studying MMP and TIMP expression levels because all tissues are remodeled under the control of one molecule, thyroid hormone. Here, using RT-PCR analysis, we examine the metamorphic RNA levels of two membrane-type MMPs (MT1-MMP, MT3-MMP), two TIMPs (TIMP-2, TIMP-3) and a potent gelatinase (Gel-A) that can be activated by the combinatory activity of a MT-MMP and a TIMP. In the metamorphic tail and intestine the RNA levels of TIMP-2 and MT1-MMP mirror each other, and closely resemble that of Gel-A as all three are elevated during periods of cell death and proliferation. Conversely, MT3-MMP and TIMP-3 do not have similar RNA level patterns nor do they mimic the RNA levels of the other genes examined. Intriguingly, TIMP-3, which has been shown to have anti-apoptotic activity, is found at low levels in tissues during periods of apoptosis.
???displayArticle.pubmedLink???
17912339
???displayArticle.pmcLink???PMC1991586 ???displayArticle.link???PLoS One
Figure 1. Schematic of Intestinal and Tail Cell Death and Cell Proliferation Events During Metamorphosis.Xenopus laevis metamorphosis begins when T3 levels elevate at stage 57 and terminates at stage 66 [26]. Top illustrations are of intestine cross-sections and are not to scale. Distances between stages are also not to scale. In response to T3 the intestine changes from a simple structure with one luminal fold (stage 56) to one with multiple folds in the post-metamorphic froglet following stage 66. As intestine metamorphosis begins ECM remodeling in the connective tissue (C) results in cell death (open circles) and cell proliferation (closed circles) of overlying epithelial cells (E). Bottom illustrations represent tail lengths during metamorphosis. Tail regression due to cell death begins at stage 62/63 and is complete by stage 66. Solid line = cell death, dashed line = cell proliferation. C = connective tissue, E = epithelial, M = muscle
Figure 2. Patterns of MMP and TIMP RNA Levels Seen during X. laevis Intestine Metamorphosis Derived From RT-PCR Data.Levels of RNA found during intestine metamorphosis demonstrated that MT1-MMP, TIMP-2 and TIMP-3 shared similar RNA expression patterns, with peaks present at stages 58 and63. MT3-MMP and MMP-2 RNA expression patterns in the intestine did mirror each other, but were not similar to the three other genes. Changes in RNA levels are not quantitative, but instead illustrate patterns of expression.
Figure 3. Representative RT-PCR Results of Similar MT1-MMP and TIMP-2 Levels of RNA During Natural and T3 Induced Metamorphosis.PCR products were agarose gel fractionated, stained, and photographed. MT1-MMP and TIMP-2 transcription patterns mimic each other at all stages and conditions. In the intestine, MT1-MMP and TIMP-2 transcripts are poorly detected at stage 56 prior to metamorphosis. Levels of both increase during stages 58, 61 and 63 and then drop to pre-metamorphic levels at stage 65. Conversely, in the tail, transcripts are detectable at stage 56, rise to stage 61, and then begin to drop at stage 63. T3 treatment induces a drop in levels after one day, but an increase after three days for both genes. EF1α RNA levels are shown for all comparable stages and treatments.
Figure 4. Patterns of MMP and TIMP RNA Levels Seen During X. laevis Tail Metamorphosis Derived From RT-PCR Data.Levels of RNA found during tail metamorphosis demonstrated that MT1-MMP, TIMP-2 and MMP-2 shared similar RNA expression patterns, peaking at stage 61 and staying elevated at stage 63. MT3-MMP and TIMP-3 expression patterns in the tail were not similar to the three other genes, nor to each other. Changes in RNA levels are not quantitative, but instead illustrate patterns of expression.
Figure 5. Patterns of MMP and TIMP RNA Levels Seen During T3 Induced Metamorphosis in X. laevis Intestine and Tail as Derived From RT-PCR Data.Levels of RNA found during induced metamorphosis of the intestine and tail demonstrated that MT1-MMP and TIMP-2 shared similar RNA expression patterns, dipping after 1 day and elevating thereafter. MMP-2 and MT3-MMP also shared similar RNA expression patterns, elevating after 1 day in both the intestine and tail. TIMP-3 expression patterns were not similar between the intestine and tail, nor were they similar to the four other genes. Changes in RNA levels are not quantitative, but instead illustrate patterns of expression.
Arvelo,
[Metalloproteinases in tumor progression. Review].
2006, Pubmed
Arvelo,
[Metalloproteinases in tumor progression. Review].
2006,
Pubmed
Crump,
Exposure to the herbicide acetochlor alters thyroid hormone-dependent gene expression and metamorphosis in Xenopus Laevis.
2002,
Pubmed
,
Xenbase
Damjanovski,
Differential regulation of three thyroid hormone-responsive matrix metalloproteinase genes implicates distinct functions during frog embryogenesis.
2000,
Pubmed
,
Xenbase
Damjanovski,
Overexpression of matrix metalloproteinases leads to lethality in transgenic Xenopus laevis: implications for tissue-dependent functions of matrix metalloproteinases during late embryonic development.
2001,
Pubmed
,
Xenbase
Damjanovski,
Spatial and temporal regulation of collagenases-3, -4, and stromelysin -3 implicates distinct functions in apoptosis and tissue remodeling during frog metamorphosis.
1999,
Pubmed
,
Xenbase
Das,
Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles.
2006,
Pubmed
,
Xenbase
Fu,
Transcriptional regulation of the Xenopus laevis Stromelysin-3 gene by thyroid hormone is mediated by a DNA element in the first intron.
2006,
Pubmed
,
Xenbase
Gross,
Specific degradation of the collagen molecule by tadpole collagenolytic enzyme.
1965,
Pubmed
Hammoud,
Cloning and developmental characterization of Xenopus laevis membrane type-3 matrix metalloproteinase (MT3-MMP).
2006,
Pubmed
,
Xenbase
Hasebe,
Spatial and temporal expression profiles suggest the involvement of gelatinase A and membrane type 1 matrix metalloproteinase in amphibian metamorphosis.
2006,
Pubmed
,
Xenbase
Hasebe,
Evidence for a cooperative role of gelatinase A and membrane type-1 matrix metalloproteinase during Xenopus laevis development.
2007,
Pubmed
,
Xenbase
Ishizuya-Oka,
Requirement for matrix metalloproteinase stromelysin-3 in cell migration and apoptosis during tissue remodeling in Xenopus laevis.
2000,
Pubmed
,
Xenbase
Ishizuya-Oka,
Thyroid hormone-induced expression of sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine.
2001,
Pubmed
,
Xenbase
Jung,
Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone-induced tail resorption.
2002,
Pubmed
,
Xenbase
Kang,
Activation of membrane-type matrix metalloproteinase 3 zymogen by the proprotein convertase furin in the trans-Golgi network.
2002,
Pubmed
Lambert,
TIMPs as multifacial proteins.
2004,
Pubmed
Nagase,
Structure and function of matrix metalloproteinases and TIMPs.
2006,
Pubmed
Pickard,
Overexpression of the tissue inhibitor of metalloproteinase-3 during Xenopus embryogenesis affects head and axial tissue formation.
2004,
Pubmed
,
Xenbase
Shi,
Thyroid hormone regulation of apoptotic tissue remodeling: implications from molecular analysis of amphibian metamorphosis.
2001,
Pubmed
,
Xenbase
Shi,
Auto-regulation of thyroid hormone receptor genes during metamorphosis: roles in apoptosis and cell proliferation.
1998,
Pubmed
,
Xenbase
Somiari,
Plasma concentration and activity of matrix metalloproteinase 2 and 9 in patients with breast disease, breast cancer and at risk of developing breast cancer.
2006,
Pubmed
Sternlicht,
How matrix metalloproteinases regulate cell behavior.
2001,
Pubmed
Walsh,
Soluble membrane-type 3 matrix metalloprioteinase causes changes in gene expression and increased gelatinase activity during Xenopus laevis development.
2007,
Pubmed
,
Xenbase
