Researchers in Finland have identified a protein called AMPK as a possible new target for therapies aimed to treat pulmonary fibrosis and other fibrotic diseases.
Their study, “AMPK Negatively Regulates Tensin-Dependent Integrin Activity,” appeared in The Journal of Cell Biology.
In human tissues, the space between adjacent cells, called the extracellular matrix, is filled with many different proteins and molecules that regulate cellular proximity and interaction. Among these “adhesion molecules” is group of proteins called integrins that permit the cells’ interior compartment to communicate with the extracellular matrix. However, too much matrix formation promotes fibrosis, which in turn contributes to diseases like pulmonary fibrosis.
In their study, researchers at Finland’s Turku Centre for Biotechnology found that AMPK, which works as an energy sensor in cells, influences integrin activity and thus, adhesion between cells.
They observed that loss of AMPK promotes integrin activity (increased adhesion) and matrix production through activation of the tensin protein. In these conditions, cells can generate more mechanical stress and spread. When present, AMPK inhibits the expression of the integrin-binding proteins tensin1 and tensin3, which block all these effects.
“This is a significant finding, since the rather cheap and widely used drug called metformin activates the AMPK sensor in particular and inhibits diabetes, cancer, fibrosis and cardiovascular diseases, and promotes longevity,” Johanna Ivaska, the study’s senior author, said in a news release. “Our discovery opens up new therapeutic opportunities for the treatment of these diseases.”
Together, the results showed that AMPK regulates cells’ interaction with each other and with the extracellular matrix, as well as its capacity to expand in tissues.
“Our aim was to identify potential novel targets to treat diseases associated with excessive matrix formation, such as cancer and fibrotic diseases which are major causes of morbidity and mortality worldwide,” said the study’s first author, Maria Georgiadou.
“AMPK is known to control energy homeostasis,” Georgiadou added. “In our study, we have shown that this fuel sensor can also regulate integrin signaling and matrix formation, suggesting that AMPK serves as a general master switch in our body.”