Activation of key developmental pathway may lead to increase in lung stem cells

London, June 18 : Researchers at University of Pennsylvania School of Medicine have discovered that a molecular pathway vital for stem cell and developmental biology, called the Wnt pathway, may lead to an increase in lung stem cells when activated.

The study also found that, if put to use, this knowledge may help in developing therapies for lung-tissue repair after injury or disease.

"The current findings show that increased activity of the Wnt pathway leads to expansion of a type of lung stem cell called bronchioalveolar stem cells," Nature quoted senior author Edward Morrisey, Ph.D., Associate Professor of Medicine and Cell and Developmental Biology, as saying.

"This information will give us a more extensive basic understanding of Wnt signaling in adult tissue repair in the lung and other tissues and also start to help us determine whether pharmacological activation or inhibition of this pathway can be utilized for treatments," explained Morrisey, who is also the Scientific Director of the Penn Institute for Regenerative Medicine.

The researchers said that activation of the Wnt signaling pathway facilitates the expansion, or increase in number, of bronchioalveolar stem cells in the lung. Wnt signalling is inhibited by a protein called GATA6, that makes it possible by directly regulating the expression of another protein in the Wnt pathway called frizzled 2 (Fzd2).

They stressed that Wnt signaling is an important pathway in stem cell biology. They said the finding that GATA6 negatively regulates Wnt signaling and that GATA6 is also vital in embryonic stem cell replication and differentiation, indicates that these two pathways not only lib ked to lung stem cells but in other tissues where they play important roles including the heart, gut, and pancreas.

"We were surprised by the robust activation of Wnt signaling after loss of GATA6 expression in the lung. Such a robust activation is rarely observed," said Morrisey.

It is possible to pharmacologically modulate Wnt signaling with the help of compounds, including lithium. Also, the use of such compounds may facilitate forced expansion and differentiation of key stem cell populations in the lung and other tissues for adult tissue repair after injury or disease.

The findings of this study are published online in advance of print publication in Nature Genetics.

ANI