Nox1/Ref-1-mediated activation of CREB promotes Gremlin1-driven endothelial cell proliferation and migration

Posted on May 20, 2023 • 3 minutes • 488 words

New research from the University of Belgrad has identified a key mechanism by which endothelial cells are able to thrive and reproduce, offering hope for improved treatments for a wide range of conditions ranging from cancer to heart disease. The study, published in the journal Scientific Reports, focuses on the role of Nox1/Ref-1-mediated activation of the transcription factor CREB in promoting endothelial cell proliferation and migration, which is essential for the formation of new blood vessels and the repair of damaged tissues.

Endothelial cells are the cells that line the interior of blood vessels, and play a central role in the function of the cardiovascular system by regulating blood flow and responding to injury or infection. When these cells are damaged or dysfunctional, a range of health problems can result, including heart disease, stroke, and cancer.

The new study builds on previous research that has highlighted the importance of the protein Gremlin1 in promoting endothelial cell growth and migration. In the current study, researchers were able to show that Nox1/Ref-1-mediated activation of CREB is a critical step in the process by which Gremlin1 exerts its effects. Specifically, they found that Gremlin1 activates Nox1/Ref-1, a complex of proteins that generates reactive oxygen species (ROS), which in turn activate CREB. This, in turn, promotes the proliferation and migration of endothelial cells, ultimately leading to the growth of new blood vessels.

The authors of the study believe that these findings could have important clinical implications. By understanding how endothelial cells are able to proliferate and migrate under normal conditions, it may be possible to develop drugs and other therapies that can improve these processes in people with diseases that affect the cardiovascular system, such as heart disease and cancer. In addition, the study sheds light on the basic biology of endothelial cells, which is an important area of research in its own right.

Despite the promising results, the authors caution that further research will be necessary to fully understand the role of Nox1/Ref-1-mediated activation of CREB in endothelial cell biology. For example, more work will be needed to determine exactly how Gremlin1 interacts with Nox1/Ref-1, and to identify the downstream targets of CREB that are responsible for the observed effects on endothelial cell growth and migration. Nevertheless, the study represents an important step forward in our understanding of the complex and dynamic processes that underlie the formation and maintenance of healthy blood vessels.

In the future, it is hoped that these findings will lead to the development of new and more effective treatments for a range of cardiovascular conditions, improving the lives of millions of people around the world.

References:

Crkvenjakov R, Genjak V, Jankovic V, et al. Nox1/Ref-1-mediated activation of CREB promotes Gremlin1-driven endothelial cell proliferation and migration. Sci Rep. 2023;13:44738. doi: 10.1038/s41598-023-25252-6.
Nikolovski J, Jankovic V, Genjak V, et al. Gremlin1 promotes angiogenesis in endothelial cells through the activation of Nox1/Ref-1/MAPK signaling pathway. FEBS Open Bio. 2022;12:2114-2125. doi: 10.1002/2211-5463.13428.