ArticleThe Journal of clinical investigation2011
Heparanase powers a chronic inflammatory circuit that promotes colitis-associated tumorigenesis in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
112 citing papers in PubMed, 187 citations in OpenAlex.
- Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.World journal of gastroenterology · 2023Trial
- Heparanase, Endothelial Dysfunction, and Cardiovascular Risk: The Emerging Role of Vitamin D.ACS pharmacology & translational science · 2026Review
- The emerging role of heparanase in cardiovascular diseases: Pathophysiology, clinical outcomes, and therapeutic perspectives.Journal of thrombosis and thrombolysis · 2026Review
- Metabolic Endotoxemia Amplifies Estrogen Signaling Through Stromal Crosstalk in Obesity-Associated Breast Cancer.International journal of molecular sciences · 2026Article
- Inflammatory bowel disease and extracellular matrix: when victim becomes double agent.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Identification of potential diagnostic markers and molecular mechanisms of asthma and ulcerative colitis based on bioinformatics and machine learning.Frontiers in molecular biosciences · 2025Article
- Article
- The pressing need for study on the effects of Mpox on the progression of vascular inflammation: A well-timed call.Health science reports · 2024Article
- The Uptake of Heparanase into Mast Cells Is Regulated by Its Enzymatic Activity to Degrade Heparan Sulfate.International journal of molecular sciences · 2024Article
- How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer.Biomolecules · 2024Review
- Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection.International journal of molecular sciences · 2023Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Heparanase Modulates Chromatin Accessibility.Cells · 2023Article
- Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study.Human molecular genetics · 2023Article
- Heparanase is the possible link between monkeypox and Covid-19: robust candidature in the mystic and present perspective.AMB Express · 2023Review
- Heparanase contributes to pancreatic carcinoma progression through insulin-dependent glucose uptake.Frontiers in cell and developmental biology · 2023Article
- Role of heparanase in pulmonary hypertension.Frontiers in pharmacology · 2023Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is closely associated with colon cancer. Expression of the enzyme heparanase is clearly linked to colon carcinoma progression, but its role in UC is unknown. Here we demonstrate for what we believe to be the first time the importance of heparanase in sustaining the immune-epithelial crosstalk underlying colitis-associated tumorigenesis. Using histological specimens from UC patients and a mouse model of dextran sodium sulfate-induced colitis, we found that heparanase was constantly overexpressed and activated throughout the disease. We demonstrate, using heparanase-overexpressing transgenic mice, that heparanase overexpression markedly increased the incidence and severity of colitis-associated colonic tumors. We found that highly coordinated interactions between the epithelial compartment (contributing heparanase) and mucosal macrophages preserved chronic inflammatory conditions and created a tumor-promoting microenvironment characterized by enhanced NF-κB signaling and induction of STAT3. Our results indicate that heparanase generates a vicious cycle that powers colitis and the associated tumorigenesis: heparanase, acting synergistically with the intestinal flora, stimulates macrophage activation, while macrophages induce production (via TNF-α-dependent mechanisms) and activation (via secretion of cathepsin L) of heparanase contributed by the colon epithelium. Thus, disruption of the heparanase-driven chronic inflammatory circuit is highly relevant to the design of therapeutic interventions in colitis and the associated cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.