Molecular Pathway Linked to Lung Tissue Repair

Cell biologists seeking to develop therapies for lung-tissue repair have traced a molecular pathway that expands the population of immature stem cells and stimulates them to differentiate into mature lung tissue cells.

Investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA; www.upenn.edu) studied the Wnt signaling pathway. The Wnt pathway involves a large number of proteins that can regulate the production of Wnt signaling molecules, their interactions with receptors on target cells, and the physiological responses of target cells that result from the exposure of cells to the extracellular Wnt ligands. Although the presence and strength of any given effect depends on the Wnt ligand, cell type, and organism, some components of the signaling pathway are remarkably conserved in a wide variety of organisms, from Caenorhabditis elegans to humans. Protein homology suggests that several distinct Wnt ligands were present in the common ancestor of all bilaterian life, and certain aspects of Wnt signaling are present in sponges and even in slime molds.

Data published in the June 8, 2008, online edition of the journal Nature Genetics revealed that a protein called GATA6 inhibited Wnt signaling by directly regulating the expression of another protein in the Wnt pathway called frizzled 2 (Fzd2). The presence or absence of GATA6 determined whether stem cells increased as an undifferentiated population or whether they developed into mature lung tissue cells.

"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,” explained senior author Dr. Edward Morrisey, associate professor of medicine and cell and developmental biology at the University of Pennsylvania School of Medicine. "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.”


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