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Thread: why are matrix metalloproteinases expressed in our skin?

  1. #1
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    Default why are matrix metalloproteinases expressed in our skin?

    just wondering, we have to inhibit MMPs which play a role in angiogenesis..but why are they expressed abnormally in our skin?

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    Here is a bit of info about matrix metalloproteinases. Their function is to break down the extracellular matrix (the 'glue' between cells) during development and for maintenance and remodelling of tissues. Angiogenesis (growth of new blood vessels) is an example of a remodelling process requiring MMP activity. Normally MMPs are not expressed in the skin, except in response to wounds, in which specialized skin cells called keratinocytes need to migrate to the site of injury. This migration of cells requires changes in the extracellular matrix, so the MMPs are needed. MMP expression in the skin is triggered by inflammation in many different dermatological and gastrointestinal conditions. During tumour development MMP expression is part of the pathway leading to metastasis (the migration of tumour cells, leading to the development of secondary tumours).

    Because rosacea involves both angiogenic and inflammatory effects, MMPs are strongly activated.

    The good news is that components of green tea have been shown to inhibit expression of MMPs 2 & 9, which are the key MMPs acting in rosacea. While the effect of green tea has not been studied specifically in relation to rosacea, it is not a bad idea to give it a try. For all you coffee drinkers especially, switching from coffee to green tea should have a double benefit, as green tea is mildly alkalizing while coffee is extremely acidifying.
    All this at no cost and without side effects!


    Here is some further reading:

    Matrix metalloproteinases in skin
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Matrix metalloproteinases: pro- and anti-angiogenic activities
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Orally Administered Green Tea Polyphenols Prevent Ultraviolet Radiation-Induced Skin Cancer in Mice through Activation of Cytotoxic T Cells and Inhibition of Angiogenesis in Tumors
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

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    thanks for info, kind of funny that I have had a lot of problems with convincing a plastic surgeon to remove a mole cause I had take low dose isotretinoin 2 months earlier, then a month later he removed the mole and I had to take 200 mg doxycycline from all the waiting...I sense that the 200 mg doxycycline impaired the healing more than the 400mg isotretinoin taken earlier...so I probably did worse waiting, both for the healing of the wound and my rosacea ](*,)

    perhaps Im wrong and doxycycline has no impact on wound healing..but from you write inhibiting MMP seems to have a negative impact

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    Quote Originally Posted by alpha_waves
    from you write inhibiting MMP seems to have a negative impact
    I think perhaps the title of the second reference is a bit misleading. The experiment was to see how inhibiting MMPs affected wound healing and hypersensitivity (in chronic ulcers), as normally the MMPs are activated by wounding.

    I think you are correct in understanding that we should look for ways to inhibit MMPs in rosacea skin. However, this may affect our wound response, so perhaps it would be better to leave the MMPs to their own devices for a while in the case of mole removal to make sure the skin heals properly.

    Green tea anyone???

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    Quote Originally Posted by no more red cheeks!
    Here is a bit of info about matrix metalloproteinases. Their function is to break down the extracellular matrix (the 'glue' between cells) during development and for maintenance and remodelling of tissues. Angiogenesis (growth of new blood vessels) is an example of a remodelling process requiring MMP activity. Normally MMPs are not expressed in the skin, except in response to wounds, in which specialized skin cells called keratinocytes need to migrate to the site of injury. This migration of cells requires changes in the extracellular matrix, so the MMPs are needed. MMP expression in the skin is triggered by inflammation in many different dermatological and gastrointestinal conditions. During tumour development MMP expression is part of the pathway leading to metastasis (the migration of tumour cells, leading to the development of secondary tumours).

    Because rosacea involves both angiogenic and inflammatory effects, MMPs are strongly activated.

    The good news is that components of green tea have been shown to inhibit expression of MMPs 2 & 9, which are the key MMPs acting in rosacea. While the effect of green tea has not been studied specifically in relation to rosacea, it is not a bad idea to give it a try. For all you coffee drinkers especially, switching from coffee to green tea should have a double benefit, as green tea is mildly alkalizing while coffee is extremely acidifying.
    All this at no cost and without side effects!


    Here is some further reading:

    Matrix metalloproteinases in skin
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Matrix metalloproteinases: pro- and anti-angiogenic activities
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

    Orally Administered Green Tea Polyphenols Prevent Ultraviolet Radiation-Induced Skin Cancer in Mice through Activation of Cytotoxic T Cells and Inhibition of Angiogenesis in Tumors
    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum



    No More Red,

    Outstanding information. With this information, did you get the sense that oral green tea was more potent than topical green tea creams?

    Collagenex and the new Oracea are powerful MMP inhibitors also and have no antibacterial actions.

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    MMP-inhibitors..do they impair healing like isotretinoin?

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    Quote Originally Posted by drnase
    With this information, did you get the sense that oral green tea was more potent than topical green tea creams?
    Interesting, now reading a little more about green tea, it seems that although there are many studies showing beneficial effects of oral and topical green tea extracts (both the polyphenols and, surprisingly, the caffeine) on the skin (primarily investigating the protective effects against UV-induced carcinogenesis) through antioxidant effects, it is also possible to induce the opposite effect (creating reactive oxygen species) with the same topical green tea extracts!

    http://jpet.aspetjournals.org/cgi/co...full/307/1/230

    This study treated normal and tumour epithelial cells with a high concentration of EGCG, one of the main polyphenols of green tea, and saw that while normal cells received an anti-cancer antioxidant effect, the tumour cells actually generated excess reactive oxygen species, promoting the death of tumour cells. An interesting implication of this study is the potential to use green tea extracts in combination with chemo or radiotherapy, as healthy cells are protected while tumour cells are weakened.

    This study also showed that cells of the oral cavity and digestive tract are resistant to damage by high doses of EGCG, whereas other cells are more sensitive. This leads me to think that topical application of green tea extracts carries a higher risk than oral consumption. Drink up!

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    Quote Originally Posted by alpha_waves
    MMP-inhibitors..do they impair healing like isotretinoin?
    Isotretinoin could be considered a broad spectrum MMP inhibitor, as it acts on MMPs 2, 9 & 13 in the skin, which are produced by sebocytes (sebum-secreting cells in the sebaceous glands) and keratinocytes (cells crucial for wound healing).

    Doxycycline (including collagenex and oracea) and tetracyclines inhibit MMP2 in keratinocytes, so this class of MMP inhibitors is more specific than isotretinoin.

    MMPs 1, 2, 3, 9, 10 & 26 are the major MMPs needed for healing wounds to the skin. MMPs 1, 2, 9 & 13 are elevated in keratinocytes of inflammatory acne, while MMPs 3 & 9 are elevated in the cornea of patients with ocular rosacea, and are inhibited by doxycycline.

    The regulation of MMPs is very complex and varies in different tissues, so ideally we would find an MMP inhibitor that affects only those MMPs overexpressed in rosacea skin (or cornea), or which act only in the skin. As well as wound healing, MMPs are also a vital part of the female menstrual cycle, so inhibitors should be used with care until more is known about the overall affects on our health and well being.

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    Hi nomoreredcheeks,do you use isotretinoin???
    male,laser treatments,no skincare utilized.

  10. #10
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    No, I have never used isotretinoin. My rosacea was not as severe as many people here, so it didn't seem worth the risk. It is a very potent teratogen (toxic to the fetus) so should be used with extreme caution by women of childbearing age, even if you have no intention of becoming pregnant. There can also be other side effects such as dry skin and inflammation of the eyes (and this is to heal our skin and eyes!), liver problems, depression, joint aches, increased cholesterol, and (rarely) brain swelling.

    For the last half year I have been able to keep my rosacea under control by eating an alkalizing diet. The most likely side effects of this treatment are reduced probability of osteoperosis, heart disease, diabetes, breast, colon, prostate & lung cancers.

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