| 1. |
- Phillipson, Mia, et al.
(författare)
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The gastric mucus layers: constituents and regulation of accumulation.
- 2008
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:4, s. G806-12
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Tidskriftsartikel (refereegranskat)abstract
- The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.
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| 2. |
- Schreiber, Olof, et al.
(författare)
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iNOS-Dependent Increase in Colonic Mucus Thickness in DSS-Colitic Rats
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e71843-
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease. Methods: Colitis was induced with 5% DSS in drinking water for 8 days prior to experiment, when the descending colonic mucosa of anesthetized rats was studied using intravital microscopy. Mucus thickness was measured with micropipettes attached to a micromanipulator. To assess the contributions of NOS and prostaglandins in the regulation of colonic mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed by 3 mg/kg/h), the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3 mg/kg/h) and the non-selective COX-inhibitor diclofenac (5 mg/kg) were administered intravenously prior to experiment. To further investigate the role of iNOS in the regulation of colonic mucus thickness, iNOS -/- mice were used. Results: Colitic rats had a thicker firmly adherent mucus layer following 8 days of DSS treatment than untreated rats (88 +/- 2 mu m vs 76 +/- 1 mu m). During induction of colitis, the thickness of the colonic mucus layer initially decreased but was from day 3 significantly thicker than in untreated rats. Diclofenac reduced the mucus thickness similarly in colitic and untreated rats (-16 +/- 5 mu m vs -14 +/- 2 mu m). While L-NNA had no effect on colonic mucus thickness in DSS or untreated controls (+3 +/- 2 mm vs +3 +/- 1 mu m), L-NIL reduced the mucus thickness significantly more in colitic rats than in controls (-33 +/- 4 mu m vs -10 +/- 3 mu m). The importance of iNOS in regulating the colonic mucus thickness was confirmed in iNOS-/- mice, which had thinner colonic mucus than wild-type mice (35 +/- 3 mu m vs 50 +/- 2 mu m, respectively). Furthermore, immunohistochemistry revealed increased levels of iNOS in the colonic surface epithelium following DSS treatment. Conclusion: Both prostaglandins and nitric oxide regulate basal colonic mucus thickness. During onset of colitis, the thickness of the mucus layer is initially reduced followed by an iNOS mediated increase.
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| 3. |
- Schreiber, Olof, 1980-, et al.
(författare)
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iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease. Methods: Colitis was induced with 5% DSS for 9 days. The colon of anesthetized rats was mounted mucosal side up and studied with intravital microscopy. Using a micropipette, attached to a micromanipulator and a digimatic indicator, mucus thickness was measured. The unselective NOS inhibitor L-NNA, the selective iNOS inhibitor L-NIL and the unselective COX inhibitor diclofenac were used to assess the contributions of NOS and prostaglandins in the regulation of mucus thickness. C57Bl/6 and iNOS -/- mice were used to further investigate the role of iNOS in mucus regulation. Results: Colitic rats had a thicker firmly adherent mucus layer than untreated control rats 9 days after the start of the experiment (88 ± 2 µm vs 76 ± 1 µm). During the course of the colitis-induction the thickness of the mucus layer first decreased, but from day 4 the mucus thickness was significantly thicker than in untreated rats. Diclofenac (5 mg/kg i.v.) reduced the mucus thickness comparably in colitic and untreated rats (-17 ± 6 µm vs -14 ± 2 µm). While L-NNA had no effect on mucus thickness in either DSS or untreated controls (+3 ± 2 µm vs +3 ± 1 µm), L-NIL reduced the mucus thickness significantly more in colitic rats than in untreated controls (-33 ± 4 µm vs -12 ± 1 µm). The importance of iNOS in maintaining mucus thickness was confirmed in iNOS -/- mice which had a thinner mucus thickness than control mice (35 ± 3 µm vs 50 ± 2 µm). Conclusion: Colitic rats have a thicker firmly adherent colonic mucus layer and this effect is mediated by iNOS. Prostaglandins are involved in the regulation of base line mucus secretion.
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