IKKβ regulates endothelial thrombomodulin in a Klf2‐dependent manner

ConclusionsIKK inhibition increased TM expression and function, and attenuated TNF‐mediated TM down‐regulation. In contrast, inhibition of down‐stream canonical NF‐B protein family members p50 and p65 (RelA) failed to up‐regulate TM expression and did not affect IKK inhibition–mediated TM over‐expression. However, knockdown of cRel and RelB, family members of the canonical and non‐canonical NF‐κB pathway, respectively, resulted in TM over‐expression. IKK inhibition caused over‐expression, increased promoter activity and enhanced binding of Krüppel‐like factor 2 (Klf2) to the TM promoter, which positively regulates TM expression. Finally, knockdown of Klf2 completely attenuated IKKβ inhibition‐mediated TM up‐regulation. We conclude that IKK regulates TM in a Klf2‐dependent manner.This article is protected by copyright. All rights reserved.
Source: Journal of Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Original Article ‐ Coagulation Source Type: research