Thbd-flox Mouse

Thbd, also known as thrombomodulin, is a key component of the anticoagulant protein C-system, acting at the endothelium. It is involved in anti-inflammatory and barrier-stabilizing processes, playing a significant role in maintaining hemostatic balance [1].

In a mouse model where the middle cerebral artery was occluded to induce ischemic brain damage, endothelial expression of Thbd increased in the peri-infarct area while decreasing in the core of the ischemic tissue compared to the contralateral side. Inducible deletion of Thbd specifically in brain endothelial cells worsened stroke outcome 48 hours after occlusion, with decreased vessel diameters and impaired angiogenesis in the peri-infarct area, indicating its role in enhancing vessel diameter and proliferation during ischemic stroke [1].

In another study, in mouse models of NASH, inhibiting the Thbd-PAR1 signaling axis with vorapaxar reduced the burden of senescent hepatocytes and improved NASH and fibrosis, suggesting that this signaling axis is a novel therapeutic target for NASH [2].

In conclusion, Thbd is crucial for maintaining hemostasis, anti-inflammation, and endothelial-related functions. Mouse models, especially those with inducible deletion of Thbd, have revealed its significance in ischemic stroke and NASH. These findings provide valuable insights into the role of Thbd in disease processes and potential therapeutic targets.