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: R. Pathak, L. Shao, S. M. Chafekar, W. Feng, U. Ponnappan, L.M. Fink, D. Zhou, M. Hauer‐Jensen Tags: Original Article ‐ Coagulation Source Type: research