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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 - PLoS ONE (2007)

Bottom Line: 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.Intriguingly, TIMP-3, which has been shown to have anti-apoptotic activity, is found at low levels in tissues during periods of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Western Ontario, London, Ontario, Canada.

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.

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Related in: MedlinePlus

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.
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pone-0001000-g004: 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.

Mentions: The RNA levels of the five genes were distinct during tail metamorphosis versus the metamorphic intestine (compare Figure 2 and Figure 4). MT3-MMP RNA displayed one peak at stage 61, while TIMP-3 RNA levels dipped at stage 61. MT1-MMP, TIMP-2 and Gel-A RNA levels increased as metamorphosis progressed and were maintained until the end of metamorphosis. Metamorphosis of the tail is a late event and one of the last to occur as all tail tissues are remodeled and removed in an efficient and safe manner. MMPs (Stromelysin-3, as well as collagenase-3 and –4) have already been shown to be expressed in distinct tail domains [3] and here high levels of MT1-MMP, MT3-MMP and Gel-A also support the role for these MMPs in tail resorption. The high levels of TIMP-2 supports two possible roles for this molecule. It can either work with MT1-MMP in activating other pro-MMPs, or conversely, if protein levels are high enough, TIMP-2 can inhibit and slow ECM remodeling to allow tail resorption to take place. TIMP-3 may then be playing an important role in modulating the speed of ECM degradation at late stages of metamorphosis (after stage 63), presumably a time when many MMPs are active and would otherwise degrade the ECM and induce apoptosis.


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 - PLoS ONE (2007)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1991586&req=5

pone-0001000-g004: 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.
Mentions: The RNA levels of the five genes were distinct during tail metamorphosis versus the metamorphic intestine (compare Figure 2 and Figure 4). MT3-MMP RNA displayed one peak at stage 61, while TIMP-3 RNA levels dipped at stage 61. MT1-MMP, TIMP-2 and Gel-A RNA levels increased as metamorphosis progressed and were maintained until the end of metamorphosis. Metamorphosis of the tail is a late event and one of the last to occur as all tail tissues are remodeled and removed in an efficient and safe manner. MMPs (Stromelysin-3, as well as collagenase-3 and –4) have already been shown to be expressed in distinct tail domains [3] and here high levels of MT1-MMP, MT3-MMP and Gel-A also support the role for these MMPs in tail resorption. The high levels of TIMP-2 supports two possible roles for this molecule. It can either work with MT1-MMP in activating other pro-MMPs, or conversely, if protein levels are high enough, TIMP-2 can inhibit and slow ECM remodeling to allow tail resorption to take place. TIMP-3 may then be playing an important role in modulating the speed of ECM degradation at late stages of metamorphosis (after stage 63), presumably a time when many MMPs are active and would otherwise degrade the ECM and induce apoptosis.

Bottom Line: 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.Intriguingly, TIMP-3, which has been shown to have anti-apoptotic activity, is found at low levels in tissues during periods of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Western Ontario, London, Ontario, Canada.

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.

Show MeSH
Related in: MedlinePlus