A study led by Osaka University, Japan shows that TAK1 can be used to avoid apoptosis and preserve the survival of endothelial cells in an inflammatory environment.
The process of apoptosis, or cell death, is an important aspect of tissue homeostasis, as well as inflammation and disease pathogenesis related to tumour growth, infection and injury. Tumour necrosis factor-a (TNFa) is responsible for the coordination of apoptosis in a variety of tissues. However, endothelial cells in blood vessels show a unique resistance to TNFa action, which has been poorly understood until now.
Why is TNFa- induced apoptosis resisted in endothelial cells?
In endothelial cells, TNFa-induced apoptosis is tightly regulated and resisted. These cells use TNFa exposure as a signal to exit their stationary state and become active to begin inflammation. This mechanism behind this has previously remained unclear.
Testing the endothelial cells in mice
The researchers used a unique type of mouse in which TAK1 can be detected in specific tissues to show that TAK1 is an essential component in ensuring the survival of endothelial cells during inflammation and injury.
Corresponding author Nobuyuki Takakura, said: “We found that deletion of TAK1 blocked the ability of intestinal endothelial cells to disregard monocyte and macrophage inflammatory TNFα signalling induced by intestinal microbiota, resulting in haemorrhage within the intestine and liver. Thus, the presence of TAK1 safeguarded the survival of endothelial cells in these tissues.”
Hisamichi Naito, the lead author, added: “We suspected that inflammation in tumour tissues may be a powerful weapon to destroy tumor vasculature. We found that, in tumour in which TNFα is expressed abundantly, localized deletion of TAK1 resulted endothelial cell death and thereby tumor regression, suggesting that TAK1 may be a useful target in anti-angiogenic therapy.”
The study has provided a clearer understanding of endothelial cell survival during inflammation and has revealed a potential pathway for other cell types to avoid the onset of apoptosis. This finding may be important in future regenerative medicine therapies.