We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
RANDOX LABORATORIES

Download Mobile App




Experimental Treatment Eases Symptoms of IBD in Model

By LabMedica International staff writers
Posted on 01 Apr 2019
Print article
Image: The cells that line the gut of an ulcerative colitis patient are inflamed and filled with PAI-1 protein (shown in red), which is linked to blood clotting. Nuclei are shown in blue, and other intestinal cells are marked in green (Photo courtesy of Gerard Kaiko, Washington University School of Medicine).
Image: The cells that line the gut of an ulcerative colitis patient are inflamed and filled with PAI-1 protein (shown in red), which is linked to blood clotting. Nuclei are shown in blue, and other intestinal cells are marked in green (Photo courtesy of Gerard Kaiko, Washington University School of Medicine).
A recent paper described the use of an experimental enzyme inhibitor to treat and relieve symptoms of inflammatory bowel disease (IBD) in a mouse model.

Only a minority of patients with IBD responds to therapy. Thus, there is an urgent need to identify pathways in IBD to classify patient disease activity, stratify patients that will benefit from targeted therapies such as anti-tumor necrosis factor (TNF), and identify new therapeutic targets.

To this end, investigators at Washington University School of Medicine (St. Louis, MO, USA) conducted global transcriptome analyses of 1,800 intestinal biopsies from 14 independent, publicly available IBD datasets to identify IBD-related pathways. The results pointed to the coagulation gene pathway as one of the most enriched gene sets in patients with IBD.

The investigators reported in the March 6, 2019, online edition of the journal Science Translational Medicine that by using this gene-network analysis they found that, among the coagulation pathway genes, plasminogen activator inhibitor-1 (PAI-1) expression was highly enriched in active disease and in patients with IBD who did not respond to anti-TNF biologic therapy.

Plasminogen activator inhibitor-1 (PAI-1) also known as serpin E1 is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis. PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and fibrinolysis.

The investigators found that intestinal epithelial cells produced tPA, which was protective against chemical and mechanical-mediated colonic injury in mice. In contrast, PAI-1 exacerbated mucosal damage by blocking tPA-mediated cleavage and activation of anti-inflammatory TGF-beta, whereas the inhibition of PAI-1 reduced both mucosal damage and inflammation. Treatment of mice showing IBD-like symptoms with the PAI-1 inhibitor MDI-2268 blocked the inflammatory activity of the protein, and the health of the mice improved. The animals lost less weight, and their intestines showed less destruction and inflammation than mice that were treated with a placebo.

"There is a lot of interest in novel therapeutic approaches for IBD because inhibiting inflammatory molecules does not work for all patients," said senior author Dr. Thaddeus S. Stappenbeck, professor of laboratory and genomic medicine at Washington University School of Medicine. "We found a unique target that is not an inflammatory molecule, and yet blocking it reduces inflammation and signs of disease, at least in mice. If further research bears out our findings, we think this target could be helpful to a greater number of patients. What is most exciting here is that SERPINE-1 and its protein seems to be most highly expressed in people with the most severe disease and those who do not respond to immunosuppressive biologics. No one has ever thought of targeting something like this. But here we have found something that might help lots of people with IBD, especially the ones who are not benefiting much from current therapies."

Related Links:
Washington University School of Medicine

New
Platinum Member
Flu SARS-CoV-2 Combo Test
OSOM® Flu SARS-CoV-2 Combo Test
Magnetic Bead Separation Modules
MAG and HEATMAG
Anti-Cyclic Citrullinated Peptide Test
GPP-100 Anti-CCP Kit
Gold Member
TORCH Panel Rapid Test
Rapid TORCH Panel Test

Print article
77 ELEKTRONIKA

Channels

Clinical Chemistry

view channel
Image: PhD student and first author Tarek Eissa has analyzed thousands of molecular fingerprints (Photo courtesy of Thorsten Naeser / MPQ / Attoworld)

Screening Tool Detects Multiple Health Conditions from Single Blood Drop

Infrared spectroscopy, a method using infrared light to study the molecular composition of substances, has been a foundational tool in chemistry for decades, functioning similarly to a molecular fingerprinting... Read more

Molecular Diagnostics

view channel
Image: Protein ‘signatures’ obtained via a blood sample can be used to predict the onset of 67 diseases (Photo courtesy of Queen Mary University of London)

Protein Signatures in Blood Can Predict Risk of Developing More Than 60 Diseases

Measuring specific proteins to diagnose conditions like heart attacks, where troponin is tested, is a well-established clinical practice. Now, new research highlights the broader potential of protein measurements... Read more

Hematology

view channel
Image: The Truvian diagnostic platform combines clinical chemistry, immunoassay and hematology testing in a single run (Photo courtesy of Truvian Health)

Automated Benchtop System to Bring Blood Testing To Anyone, Anywhere

Almost all medical decisions are dependent upon laboratory test results, which are essential for disease prevention and the management of chronic illnesses. However, routine blood testing remains limited worldwide.... Read more

Microbiology

view channel
Image: The Simplexa C. auris direct kit is a real-time polymerase chain reaction assay run on the LIAISON MDX instrument (Photo courtesy of Diasorin)

Novel Molecular Test to Help Prevent and Control Multi Drug-Resistant Fungal Pathogen in Healthcare Settings

Candida auris (C. auris) is a rapidly emerging multi drug-resistant fungal pathogen that is commonly found in healthcare environments, where it presents a challenge due to its ability to asymptomatically... Read more

Pathology

view channel
Image: The tool can improve precision oncology by accurately predicting molecular subtypes and therapy responses (Photo courtesy of Shutterstock)

Computational Tool Integrates Transcriptomic Data for Improved Breast Cancer Diagnosis and Treatment

Breast cancer is the most commonly diagnosed cancer globally, presenting in various subtypes that require precise identification for effective, personalized treatment. Traditionally, cancer subtyping has... Read more

Industry

view channel
Image: Beckman Coulter will utilize the ALZpath pTau217 antibody to detect key biomarker for Alzheimer\'s disease on its DxI 9000 immunoassay analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter Licenses Alzpath's Proprietary P-tau 217 Antibody to Develop Alzheimer's Blood Test

Cognitive assessments have traditionally been the primary method for diagnosing Alzheimer’s disease, but this approach has its limitations as symptoms become apparent only after significant brain changes... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.