(American Journal of Pathology. 1999;155:493-503.)
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Fibrogenesis and Fibrolysis in Collagenous Colitis
Patterns of Procollagen Types I and IV,Matrix-Metalloproteinase-1 and -13, and TIMP-1 Gene Expression
Ute Günther*, Detlef Schuppan, Michael Bauer, Harald Matthes*, Andreas Stallmach§, Annette Schmitt-Gräff, Ernst-Otto Riecken* and Hermann Herbst||
From the Department of Gastroenterology*
and Institute of Pathology,
University Hospital Benjamin Franklin, Free University; Berlin; the Department of Gastroenterology,
University of Erlangen, Erlangen; the Department of Internal Medicine II,§
University Hospital, Homburg/Saar; the Institute of Pathology,
University of Freiburg im Breisgau; and the Institute of Pathology,||
University Hospital Eppendorf, Hamburg, Germany
Collagenous colitis is characterized by the deposition of a superficial subepithelial collagenous layer, the pathogenesis of which is unknown. Because the excess matrix deposition is potentially reversible, a labile imbalance between fibrogenesis and fibrolysis may be suspected. Expression of procollagen 1(I) and 1(IV), matrix-metalloproteinase (MMP)-1 and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 genes was semiquantitated by in situ hybridization on serial biopsies of 12 patients with collagenous colitis and compared to controls. Collagen types I, III, IV, and VI, tenascin, undulin/collagen XIV, and -actin were localized by immunohistology. The superficial collagen layer stained strongly for collagen types I, III, and VI, and particularly for tenascin, but not for undulin. Elevated procollagen 1(I), procollagen 1(IV), and TIMP-1 transcript levels were found in -actin-positive cells with linear distribution underneath the superficial collagenous layer, whereas MMP-1 RNA expression was variable and restricted to cell clusters. MMP-13 expression was undetectable. The patterns of procollagen 1(I)- and 1(IV)-specific labeling, combined with an intense tenascin- but absent undulin-specific staining, indicate deposition of an immature interstitial matrix that may be susceptible to degradation. The restricted MMP-1 RNA expression, counteracted by increased TIMP-1 expression, suggests locally impaired fibrolysis as a relevant factor in the pathogenesis of collagenous colitis.
Fibrogenesis and Fibrolysis in Collagenous Colitis
Moderators: Rosie, Jean, CAMary, moremuscle, JFR, Dee, xet, Peggy, Matthew, Gabes-Apg, grannyh, Gloria, Mars, starfire, Polly, Joefnh, mbeezie
Fibrogenesis and Fibrolysis in Collagenous Colitis
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
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moremuscle
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- Joined: Wed May 25, 2005 6:16 am
- Location: South Carolina
I've gotta go run some errands for a while. I'll try to shed some light on this article later today, when I get back.
Love,
Tex
Love,
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
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moremuscle
- Rockhopper Penguin
- Posts: 706
- Joined: Wed May 25, 2005 6:16 am
- Location: South Carolina
Hi Karen,
A thousand apologies. If I didn't live so far from South Carolina, I'd look you up, so that you could personally kick my butt. There's so much going on most days, that my promise to elucidate that article completely slipped my mind. Please forgive me.
Basically, Fibrogenesis refers to the creation of fibers, (as in blood clotting, for example), and Fibrolysis refers to the destruction of fibers. (Fibrosis, incidentally, refers to the development in an organ, of excess fibrous connective tissue.)
In a nutshell, what the artile is suggesting, (if I understand it correctly), is that the excess collagen deposits, that are considered to be markers of collagenous colitis, may be caused by an imbalance between fibrogenesis and fibrolysis. IOW, the build up of excess collagen in the epithelia of the colon, may be due to locally impaired fibrolysis.
I'm not at all familiar with the mechanisms of fibrogenesis, but apparently this is a normal process that is always taking place in body tissues. Normally, though, it's effects are kept in check, by fibrolysis. If fibrolysis is inadequate, then a build up of collagen results. This is apparently a different process from fibrosis, in which excess fiber is produced.
That's my take on the article. If I haven't explained myself clearly, or if you think that I have misinterpreted the authors' intent, please comment.
Love,
Wayne
A thousand apologies. If I didn't live so far from South Carolina, I'd look you up, so that you could personally kick my butt. There's so much going on most days, that my promise to elucidate that article completely slipped my mind. Please forgive me.
Basically, Fibrogenesis refers to the creation of fibers, (as in blood clotting, for example), and Fibrolysis refers to the destruction of fibers. (Fibrosis, incidentally, refers to the development in an organ, of excess fibrous connective tissue.)
In a nutshell, what the artile is suggesting, (if I understand it correctly), is that the excess collagen deposits, that are considered to be markers of collagenous colitis, may be caused by an imbalance between fibrogenesis and fibrolysis. IOW, the build up of excess collagen in the epithelia of the colon, may be due to locally impaired fibrolysis.
I'm not at all familiar with the mechanisms of fibrogenesis, but apparently this is a normal process that is always taking place in body tissues. Normally, though, it's effects are kept in check, by fibrolysis. If fibrolysis is inadequate, then a build up of collagen results. This is apparently a different process from fibrosis, in which excess fiber is produced.
That's my take on the article. If I haven't explained myself clearly, or if you think that I have misinterpreted the authors' intent, please comment.
Love,
Wayne
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
-
moremuscle
- Rockhopper Penguin
- Posts: 706
- Joined: Wed May 25, 2005 6:16 am
- Location: South Carolina
Hi Wayne -
Here is the BOOT - now, do you feel better LOL!! No reason to beat yourself up about this. It's a minor issue....
Your explanation makes complete sense. I actually believe that all disease is caused by an imbalance so it doesn't surprise me to see this explanation; that the buildup of collagen in certain areas of the colon (subepithelial? another term I don't quite understand) - locally as opposed to covering the entire wall of the colon is caused by an imbalance. What I didn't know is the mentioned ongoing processes of fibrogenesis and fibrolysis in those layers of the colon. The imbalance results in too much fiber; in this case too much collagen, right? To me that explains in new terms what is happening in the colon (wall) when we have Collagenous Colitis however, it doesn't explain what causes the imbalance.
I question and have "always" questioned the reason that doctors like to name our disease Microscopic Colitis when to me it seems that MC is actually an effect of some other underlying causes. Treating MC is not going to remove the underlying causes - it may just remove the excess collagen for a few weeks until the imbalance in the fybrogenesis/fybrolysis manifest again. I would like to see an attempt from the doctors to actually focus on finding/understanding the underlying cause(s) so the treatment can be targeted at the cause.
I find that looking at the immune system and it's reaction to certain proteins in the diet seems a likely place to find the cause for the chain reaction that lead to the development of excess collagen in the colon. Or like you have mentioned so many times before the "Leaky gut syndrom" could be where the chain reaction started.
2 cents worth of speculation on my part.
Love,
Karen
Here is the BOOT - now, do you feel better LOL!! No reason to beat yourself up about this. It's a minor issue....
Your explanation makes complete sense. I actually believe that all disease is caused by an imbalance so it doesn't surprise me to see this explanation; that the buildup of collagen in certain areas of the colon (subepithelial? another term I don't quite understand) - locally as opposed to covering the entire wall of the colon is caused by an imbalance. What I didn't know is the mentioned ongoing processes of fibrogenesis and fibrolysis in those layers of the colon. The imbalance results in too much fiber; in this case too much collagen, right? To me that explains in new terms what is happening in the colon (wall) when we have Collagenous Colitis however, it doesn't explain what causes the imbalance.
I question and have "always" questioned the reason that doctors like to name our disease Microscopic Colitis when to me it seems that MC is actually an effect of some other underlying causes. Treating MC is not going to remove the underlying causes - it may just remove the excess collagen for a few weeks until the imbalance in the fybrogenesis/fybrolysis manifest again. I would like to see an attempt from the doctors to actually focus on finding/understanding the underlying cause(s) so the treatment can be targeted at the cause.
I find that looking at the immune system and it's reaction to certain proteins in the diet seems a likely place to find the cause for the chain reaction that lead to the development of excess collagen in the colon. Or like you have mentioned so many times before the "Leaky gut syndrom" could be where the chain reaction started.
2 cents worth of speculation on my part.
Love,
Karen
Not sure this is the right place for this explanation but I'm going to post it anyway.
Intestinal Gluten Receptor Is Gateway for Celiac Disease
Finding could offer new treatments for other autoimmune disorders, study says
Posted July 24, 2008
THURSDAY, July 24 (HealthDay News) -- Researchers believe they have finally answered a basic question about the cause of celiac disease -- where in the body does the wheat protein gluten enter one's system?
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Video: Health News & Features
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A study published in the July issue of Gastroenterology identifies the CXCR3 receptor in the intestine as a gluten gateway. When people with celiac disease eat gluten, the protein triggers their immune system to attack the body, causing a wide range of serious health problems.
"This is a scientific question that had never been answered before," Dr. Alessio Fasano, medical director of the Center for Celiac Research at the University of Maryland School of Medicine, said in an university news release. "It is not only significant in the basic science of autoimmune disorders such as celiac disease, but in therapeutic approaches for the future. This opens a new scientific paradigm for the study of immunity."
The research team found that gliadin, the part of gluten that causes the most trouble for those with celiac disease, binds to the CXCR3 receptor. This results in the release of zonulin, a human protein that lowers the intestinal barrier to make it more permeable. While this effect is temporary in most people, the barrier stays down for long periods of time in people with celiac disease, causing disruption in the body's system.
The finding may help in research on the cause and treatment for other autoimmune diseases, Fasano said. People with type 1 diabetes and multiple sclerosis may experience a similar condition in which offending antigens enter the body through this gateway in the intestines.
"For the first time, we have evidence of how the foreign antigen gains access to the body, causing the autoimmune response," said Fasano, who is also a pediatric gastroenterologist at the University of Maryland Medical Center. "Further study is needed, but this could allow us to intervene before the zonulin is either released or activated, preventing the immune response altogether."
Intestinal Gluten Receptor Is Gateway for Celiac Disease
Finding could offer new treatments for other autoimmune disorders, study says
Posted July 24, 2008
THURSDAY, July 24 (HealthDay News) -- Researchers believe they have finally answered a basic question about the cause of celiac disease -- where in the body does the wheat protein gluten enter one's system?
Related News
Video: Health News & Features
Join a Discussion
More from Health
A study published in the July issue of Gastroenterology identifies the CXCR3 receptor in the intestine as a gluten gateway. When people with celiac disease eat gluten, the protein triggers their immune system to attack the body, causing a wide range of serious health problems.
"This is a scientific question that had never been answered before," Dr. Alessio Fasano, medical director of the Center for Celiac Research at the University of Maryland School of Medicine, said in an university news release. "It is not only significant in the basic science of autoimmune disorders such as celiac disease, but in therapeutic approaches for the future. This opens a new scientific paradigm for the study of immunity."
The research team found that gliadin, the part of gluten that causes the most trouble for those with celiac disease, binds to the CXCR3 receptor. This results in the release of zonulin, a human protein that lowers the intestinal barrier to make it more permeable. While this effect is temporary in most people, the barrier stays down for long periods of time in people with celiac disease, causing disruption in the body's system.
The finding may help in research on the cause and treatment for other autoimmune diseases, Fasano said. People with type 1 diabetes and multiple sclerosis may experience a similar condition in which offending antigens enter the body through this gateway in the intestines.
"For the first time, we have evidence of how the foreign antigen gains access to the body, causing the autoimmune response," said Fasano, who is also a pediatric gastroenterologist at the University of Maryland Medical Center. "Further study is needed, but this could allow us to intervene before the zonulin is either released or activated, preventing the immune response altogether."
"What the heart gives away is never gone ... It is kept in the hearts of others."
Here is what I've gathered up on zonulin... not only does zonulin control the intestinal barrier but also the blood brain barrier... which may have some bearing in MS or other neurological disease processes.
http://jccglutenfree.googlepages.com/zonulin
http://jccglutenfree.googlepages.com/zonulin