Angiopoietin/Tek-systemet i hälsa och sjukdom

Tidsperiod: 2013-01-01 till 2015-12-31

Projektledare: Marie Jeansson

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 2 250 000 SEK

Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) bind to the tyrosine kinase receptor, Tek, found on endothelial cells. Angpt1 is a Tek agonist and promotes endothelial cell stabilization, whereas Angpt2 is a Tek antagonist causing endothelial activation. We recently described that mice with conditional knockout of Angpt1 have aggravated fibrosis and angiogenesis in response to diabetes and wound healing. Fibrosis is a pathological process where wound repair fails to cease, even when the initial insult has been removed. There are dozens of fibrotic diseases, including heart fibrosis, atherosclerosis, asthma, cirrhosis, scleroderma and pulmonary fibrosis, accounting for an estimated 45 percent of total deaths in the US each year. I hypothesize that the Angpt/Tek system plays 3 important roles in the development of fibrosis; namely fibrogenesis, angiogenesis, and inflammation. To test my hypothesis, I will use genetic strategies in mice to assess the Angpt/Tek system in experimental models of fibrosis. According to my hypothesis, mice without Angpt1 or Tek will have faster disease progression whereas mice without Angpt2 would be protected. I am in a unique position to address this topic. First, I have generated mice with conditional Cre-inducible knockout alleles for Angpt1 and Angpt2. Second, I also have access to a Cre-inducible Tek knockout mouse as well as Cre- and rtTA- expressing mouse lines. Third, I have extensive knowledge in the methods proposed.