Crohn's Disease But Not Chronic Ulcerative Colitis Induces the Expression of PAI-1 in Enteric Neurons

Lærum, Ole Didrik; Illemann, Martin; Skarstein, A; Helgeland, Lars; Øvrebø, Kjell; Danø, Keld; Nielsen, Boye Schnack

doi:10.1111/j.1572-0241.2008.01930.x

Cited by 14 publications

(9 citation statements)

References 46 publications

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“…Interestingly, it must be pointed out that the expression of plasminogen activator inhibitor-1 (PAI-1) was increased in the duodenum of ML-infused mice. Previous reports have shown that PAI-1 expression was upregulated in neurons after experimental peripheral nerve injury [28], [29]. Taken together, both the vagus nerve recordings and PAI-1 expression suggest deregulation of the enteric nervous system following ML infusion.…”

Section: Discussionsupporting

confidence: 54%

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

Sérino

Waget

Marsollier³

et al. 2011

PLoS ONE

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BackgroundDaily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice.Methodology/Principal FindingsAn indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity.Conclusions/SignificanceLipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity.

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Section: Discussionsupporting

confidence: 54%

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

Sérino

Waget

Marsollier³

et al. 2011

PLoS ONE

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“…The inhibitory action of PAI-1 against CCK does not preclude interactions with other mediators that could be studied in the future. It is notable that intestinal PAI-1 may be increased after radiation damage [31], in experimental colitis [32], and in intestinal neurons in Crohn's disease [33]. Given that some effects of endogenous CCK on stomach function appear to be mediated by paracrine actions on intestinal vagal afferent fibres while others are mediated by actions of circulating CCK on gastric vagal afferent fibres [29], it would not be surprising if intestinal PAI-1 also played a role in modulating gastric emptying by acting locally on vagal afferent nerve fibres.…”

Section: Discussionmentioning

confidence: 99%

Plasminogen activator inhibitor (PAI)-1 suppresses inhibition of gastric emptying by cholecystokinin (CCK) in mice

Gamble

Kenny

Dockray

2013

Regulatory Peptides

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The intestinal hormone cholecystokinin (CCK) delays gastric emptying and inhibits food intake by actions on vagal afferent neurons. Recent studies suggest plasminogen activator inhibitor (PAI)-1 suppresses the effect of CCK on food intake. In this study we asked whether PAI-1 also modulated CCK effects on gastric emptying. Five minute gastric emptying of liquid test meals was studied in conscious wild type mice (C57BL/6) and in transgenic mice over-expressing PAI-1 in gastric parietal cells (PAI-1H/Kβ mice), or null for PAI-1. The effects of exogenous PAI-1 and CCK8s on gastric emptying were studied after ip administration. Intragastric peptone delayed gastric emptying in C57BL/6 mice by a mechanism sensitive to the CCK-1 receptor antagonist lorglumide. Peptone did not delay gastric emptying in PAI-1-H/Kβ mice. Exogenous CCK delayed gastric emptying of a control test meal in C57BL/6 mice and this was attenuated by administration of PAI-1; exogenous CCK had no effect on emptying in PAI-1-H/Kβ mice. Prior administration of gastrin to increase gastric PAI-1 inhibited CCK-dependent effects on gastric emptying in C57BL/6 mice but not in PAI-1 null mice. Thus, both endogenous and exogenous PAI-1 inhibit the effects of CCK (whether exogenous or endogenous) on gastric emptying. The data are compatible with emerging evidence that gastric PAI-1 modulates vagal effects of CCK.

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“…Indeed, uPAR was first identified in the colonic crypts of healthy controls and patients with IBD, without finding any difference in expression levels 16. Moreover, Laerum and colleagues located uPAR in the enteric nerves of the intestine and found increasing levels in patients with UC undergoing enteric nerve repair 17. Recently, two different works by Lönnkvist 18 and Kolho 19 evaluated soluble uPAR level in blood as a diagnostic marker for adult and paediatric IBD, respectively.…”

Section: Introductionmentioning

confidence: 99%

The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation

Genua

D’Alessio

Cibella

et al. 2014

Gut

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Crohn's Disease But Not Chronic Ulcerative Colitis Induces the Expression of PAI-1 in Enteric Neurons

Cited by 14 publications

References 46 publications

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

Plasminogen activator inhibitor (PAI)-1 suppresses inhibition of gastric emptying by cholecystokinin (CCK) in mice

The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation

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