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Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Distinct Serum and Tissue Markers Predict Fibrosis in Crohn's Disease
Ahmed Abomhya1, Ronaldo Panganiban2, Syed Adeel Hassan1,3
1Division of Digestive Diseases, Department of Internal Medicine, University of Kentucky, Lexington, KY 40506, USA.
None:
Fibrosis in Crohn's Disease (CD) occurs when there is continuous inflammation and repair mechanisms, which may lead to fibrotic strictures and ultimately intestinal surgical resection. There are limited non-invasive biomarkers for monitoring CD activity, particularly for detecting fibrosis. Thus, we set out to identify biomarkers that could be monitored for the detection and treatment of fibrosis. We used multiplex protein arrays to examine cytokines and pro-fibrotic factors in the serum of CD patients and analyzed their reliability to predict fibrosis. These markers were confirmed in tissues and the role of cytokines in upregulating fibrotic factors was examined. Collagen 1A1, Fibronectin, MMP9, and Timp-1 in patient serum were identified as strong predictors of fibrosis. IL-1β, MCP-1 and TNFα were identified as major regulators of fibrosis factors in human tissues. Overall, we identified four serum markers that are strong indicators of fibrosis and provided some novel insight into the impact of cytokines on fibrotic factors. Taken together, these findings may lead to earlier detection of fibrosis, and improved monitoring and treatment for CD patients.
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