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Kofi posted some very interesting articles on the lef group. I tried to highlight the important parts:
The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by Society for General Microbiology, via
EurekAlert!, a service of AAAS.
A possible cause of irritable bowel syndrome has been traced to a small
piece of RNA that blocks a substance protecting the colon membrane,
leading to hostile conditions that can produce diarrhea, bloating and
chronic abdominal pain; this RNA segment sends signals that stop the
activity of the gene that produces glutamine; a shortage of glutamine in
the gut is linked to the seepage of toxins and bacteria through the
intestinal wall, irritating nerves and creating disease symptoms; trying
to generate glutamine in the disordered bowel by silencing this RNA
segment could treat the diarrhea-predominant type of IBS; this form is
characterized by diarrhea and bloating as well as chronic abdominal pain
that is difficult to treat; a third of IBS patients have the
diarrhea-predominant type, another third experience consistent
constipation, and the rest experience alternating bouts of diarrhea and
constipation; in human tissue samples, the presence of this small piece
of RNA was associated with reduced activity by the gene that produces
glutamine. Lower levels of glutamine were seen only in tissue samples
from patients with the diarrhea-predominant type of IBS; a group of
these patients also had a condition called increased intestinal
permeability, which allows toxins and bacteria into the colon that
typically can't get in. The resulting irritation to nerves in the colon
is believed to contribute to diarrhea and abdominal pain; the glutamine
deficiency may be connected to the increased intestinal permeability,
which dramatically increases the likelihood that diarrhea-predominant
IBS symptoms will follow; manipulating microRNA-29a (miRNA-29a) has
potential as a novel treatment for IBS; for some patients, the pain
responds only to escalating doses of narcotics or tricyclic
antidepressants; microRNA-29a levels were four times higher in the
tissues of IBS patients with increased intestinal permeability than were
levels seen in IBS patients with normal intestinal permeability
conditions and in participants with no bowel disease; when the
microRNA-29a levels were driven up, the function of the gene that
produces glutamine was prevented and intestinal membrane permeability
increased, as well. When the microRNA-29a was artificially silenced,
gene function was active, glutamine was produced and the intestinal
membrane permeability was closer to normal; there may be other target
genes involved
<http://www.sciencedaily.com/releases/2010/08/100802110825.htm>
MicroRNA-29a regulates intestinal membrane permeability in patients with
irritable bowel syndrome; The molecular mechanisms underlying the
pathophysiology of irritable bowel syndrome (IBS) are poorly understood.
One mechanism may involve increased intestinal permeability that is
reversed with glutamine supplementation. Our goal was to evaluate the
expression of glutamine synthetase and its complementary miRNA in blood
microvesicles and gut tissues of IBS patients with increased intestinal
membrane permeability. METHODS: We evaluated 19 diarrhoea-predominant
IBS patients and 10 controls for intestinal membrane permeability using
the lactulose/mannitol method. miRNA expression was evaluated in blood
microvesicles and gut tissue. To further confirm the relationship
between miRNA and glutamine synthetase expression, cell culture
experiments were conducted. Glutamine synthetase was also evaluated in
the gut tissues of patients; A subset of patients with IBS (8/19, 42%)
had increased intestinal membrane permeability and decreased glutamine
synthetase expression compared to patients with IBS normal membrane
permeability, and to controls. Expression of miR-29a was increased in
blood microvesicles, small bowel and colon tissues of IBS patients with
increased intestinal membrane permeability. Increased intestinal
permeability was modulated by miR-29a which has a complementary site in
the 3'-UTR of the GLUL gene; GLUL regulates intestinal membrane
permeability and miR-29a regulates both GLUL and intestinal membrane
permeability. The data suggests that miR-29a effects on intestinal
membrane permeability may be due to its regulation of GLUL. Targeting
this signalling pathway could lead to a new therapeutic approach to the
treatment of patients with IBS, especially because small molecules that
mimic or inhibit miRNA-based mechanisms are readily available [PMID
19951903]
The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by Society for General Microbiology, via
EurekAlert!, a service of AAAS.
A possible cause of irritable bowel syndrome has been traced to a small
piece of RNA that blocks a substance protecting the colon membrane,
leading to hostile conditions that can produce diarrhea, bloating and
chronic abdominal pain; this RNA segment sends signals that stop the
activity of the gene that produces glutamine; a shortage of glutamine in
the gut is linked to the seepage of toxins and bacteria through the
intestinal wall, irritating nerves and creating disease symptoms; trying
to generate glutamine in the disordered bowel by silencing this RNA
segment could treat the diarrhea-predominant type of IBS; this form is
characterized by diarrhea and bloating as well as chronic abdominal pain
that is difficult to treat; a third of IBS patients have the
diarrhea-predominant type, another third experience consistent
constipation, and the rest experience alternating bouts of diarrhea and
constipation; in human tissue samples, the presence of this small piece
of RNA was associated with reduced activity by the gene that produces
glutamine. Lower levels of glutamine were seen only in tissue samples
from patients with the diarrhea-predominant type of IBS; a group of
these patients also had a condition called increased intestinal
permeability, which allows toxins and bacteria into the colon that
typically can't get in. The resulting irritation to nerves in the colon
is believed to contribute to diarrhea and abdominal pain; the glutamine
deficiency may be connected to the increased intestinal permeability,
which dramatically increases the likelihood that diarrhea-predominant
IBS symptoms will follow; manipulating microRNA-29a (miRNA-29a) has
potential as a novel treatment for IBS; for some patients, the pain
responds only to escalating doses of narcotics or tricyclic
antidepressants; microRNA-29a levels were four times higher in the
tissues of IBS patients with increased intestinal permeability than were
levels seen in IBS patients with normal intestinal permeability
conditions and in participants with no bowel disease; when the
microRNA-29a levels were driven up, the function of the gene that
produces glutamine was prevented and intestinal membrane permeability
increased, as well. When the microRNA-29a was artificially silenced,
gene function was active, glutamine was produced and the intestinal
membrane permeability was closer to normal; there may be other target
genes involved
<http://www.sciencedaily.com/releases/2010/08/100802110825.htm>
MicroRNA-29a regulates intestinal membrane permeability in patients with
irritable bowel syndrome; The molecular mechanisms underlying the
pathophysiology of irritable bowel syndrome (IBS) are poorly understood.
One mechanism may involve increased intestinal permeability that is
reversed with glutamine supplementation. Our goal was to evaluate the
expression of glutamine synthetase and its complementary miRNA in blood
microvesicles and gut tissues of IBS patients with increased intestinal
membrane permeability. METHODS: We evaluated 19 diarrhoea-predominant
IBS patients and 10 controls for intestinal membrane permeability using
the lactulose/mannitol method. miRNA expression was evaluated in blood
microvesicles and gut tissue. To further confirm the relationship
between miRNA and glutamine synthetase expression, cell culture
experiments were conducted. Glutamine synthetase was also evaluated in
the gut tissues of patients; A subset of patients with IBS (8/19, 42%)
had increased intestinal membrane permeability and decreased glutamine
synthetase expression compared to patients with IBS normal membrane
permeability, and to controls. Expression of miR-29a was increased in
blood microvesicles, small bowel and colon tissues of IBS patients with
increased intestinal membrane permeability. Increased intestinal
permeability was modulated by miR-29a which has a complementary site in
the 3'-UTR of the GLUL gene; GLUL regulates intestinal membrane
permeability and miR-29a regulates both GLUL and intestinal membrane
permeability. The data suggests that miR-29a effects on intestinal
membrane permeability may be due to its regulation of GLUL. Targeting
this signalling pathway could lead to a new therapeutic approach to the
treatment of patients with IBS, especially because small molecules that
mimic or inhibit miRNA-based mechanisms are readily available [PMID
19951903]
