In-Silico Transcriptome Analyses of Hemostasis Triggers in Inflamed Vs Normal Mucosa of IBD Patients

Background:inflammatory bowel disease (IBD) is characterized by chronic inflammation associated with an increased tendency to thrombosis and thromboembolic complications. The underlying mechanisms of VTE are not yet fully understood. Several studies reported different expressions of circulating procoagulant factors or fibrinolysis inhibitors in IBD. Others linked podoplanin overexpression with thrombosis, hypercoagulability, and increased risk of VTE. Here, we aimed to identify, among genes able to trigger thrombosis, those aberrantly expressed in IBD samples as compared with matched normal mucosa.

Methods:we analyzed the transcriptome of matched normal and inflamed lesions in 168 patients with Adult Crohn Disease (CD) and 245 pediatric IBD using publicly available datasets. We intentionally assessed the expression levels of triggers and inhibitors of the coagulation system (Tissue Factor, TFI), the fibrinolytic system (PLAU, PLAT, PAI-1/2/3, TAFI, PN-1, SERPINF2, A2M, SNX1, SERPINC1) and platelets activation (podoplanin). Analyses were finally performed using additional datasets with 219 ulcerative colitis (UC) adult patients, 198 IBD patients and compared to normal colon transciptome.

Results:in all datasets, when compared to matched normal mucosal transcriptome, CD and UC inflamed tissues over-expressed Podoplanin mRNA (p=2.46e-25). TF mRNA was also consistently up-regulated in inflamed mucosal of IBD patients, even if paralleled with up-regulation of TFPI as well, questioning on the functional role of TF in IBD. Among the regulators of the fibrinolytic system the urokinase-activator of the plasminogen is consistently deregulated in inflamed areas.

Conclusion: our in-silico analyses on gene expression profiles, using matched normal and pathological mucosa of the same patients, suggested that IBD inflamed mucosa favors platelets activation due to podoplanin over-expression. These observations require further studies to assess the biological role of podoplanin in IBD patients and opens new insights on how to perform antithrombotic prophylaxis in IBD patients.