A role for proteinase-activated receptor–1 in inflammatory bowel diseases
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Post-publication record
- Nature
- Retraction
- Reason
- Criminal Proceedings;Euphemisms for Duplication;Investigation by Company/Institution;Investigation by Third Party;Manipulation of Images;
- Date
- 7/3/2006 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation-induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.
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The record
- Venue
- Journal of Clinical Investigation
- Topic
- Blood Coagulation and Thrombosis Mechanisms
- Field
- Medicine
- Canadian institutions
- University of Calgary
- Funders
- Canadian Institutes of Health ResearchCrohn's and Colitis Foundation of CanadaCanadian Association of GastroenterologyCrohn's and Colitis FoundationUniversity of Calgary
- Keywords
- InflammationColitisInflammatory bowel diseasePathogenesisImmunologyThrombinReceptorProinflammatory cytokineGastrointestinal tractMedicineInternal medicineDiseasePlatelet
- Has abstract in OpenAlex
- yes