Yeni kas atrofisi faktörlerinin adenoviral gen aktarımı vektörleri kullanılarak farelerde incelenmesi

Cachexia is a wasting syndrome correlated with high basal energy expenditure and loss of adipose and skeletal muscle tissues. It is associated with many chronic disorders like renal failure and cancer and is an important risk factor for mortality. Currently, there is no successful therapy present to slow down or stop cachexia. We have identified several novel cachexia-related factors and studied their involvement in muscle tissue wasting. Here, we especially focused on secreted factors which promotes cellular atrophy in cultured myotubes. We developed adenoviral vectors which overexpress these proteins in cultured muscle cells and muscle tissue when injected to animals. We first tested viral vectors on cultured primary muscle cells to validate overexpression. We then purified and injected adenovirus vectors into the tibialis anterior muscles of mice. In this project, we have found that the discovered novel cachexia factor significantly increases the expression of both muscle atrophy and NFκB signaling pathway-related genes in primary myotubes and tibialis anterior muscles of mice. This new secreted factor-driven muscle atrophy is accompanied by activation of the NFκB signaling pathway shown by the increased processing of NFκB protein. Our findings suggest that targeting of this factor could be used in fighting muscle wasting associated with cancer and other chronic diseases.