Penn researchers find key developmental pathway activates lung stem
cells
Pathway could hold promise for lung tissue repair
PHILADELPHIA – Researchers from the University of Pennsylvania School
of Medicine found that the activation of a molecular pathway
important in stem cell and developmental biology leads to an increase
in lung stem cells. Harnessing this knowledge could help develop
therapies for lung-tissue repair after injury or disease. The
investigators published their findings online last week in advance of
print publication in Nature Genetics.
"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," says senior author Edward Morrisey,
Ph.D., Associate Professor of Medicine and Cell and Developmental
Biology.
"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," explains Morrisey, who is also the Scientific Director
of the Penn Institute for Regenerative Medicine.
Activation of the Wnt signaling pathway leads to expansion, or
increase in number, of bronchioalveolar stem cells in the lung. A
protein called GATA6 inhibits Wnt signaling by directly regulating
the expression of another protein in the Wnt pathway called frizzled
2 (Fzd2).
Wnt signaling is a major pathway in stem cell biology. The finding
that GATA6 negatively regulates Wnt signaling and that GATA6 has been
shown to play important roles in embryonic stem cell replication and
differentiation suggests that these two pathways are linked not only
in 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," says Morrisey. "Such a robust
activation is rarely observed."
Wnt signaling can be pharmacologically modulated with compounds,
including lithium, already approved by the FDA. Use of such
compounds, both known and newly identified through ongoing screens,
could allow for forced expansion and differentiation of key stem cell
populations in the lung and other tissues for adult tissue repair
after injury or disease.
Future directions of the Morrisey lab include not only a more
extensive basic understanding of Wnt signaling in adult-tissue repair
in the lung and other tissues, but also starting to determine whether
pharmacological activation or inhibition of this pathway can really
be utilized for treatments.
###
Penn co-authors are Yuzhen Zhang, Ashley M. Goss, Ethan David Cohen,
Rachel Kadzik, John J. Lepore, Karthika Muthukumaraswamy. Jifu Yang,
and Michael Parmacek. This work was funded by the National Institutes
of Health.
PENN Medicine is a $3.5 billion enterprise dedicated to the related
missions of medical education, biomedical research, and excellence in
patient care. PENN Medicine consists of the University of
Pennsylvania School of Medicine (founded in 1765 as the nation's
first medical school) and the University of Pennsylvania Health
System.
Penn's School of Medicine is currently ranked #4 in the nation in
U.S.News & World Report's survey of top research-oriented medical
schools; and, according to most recent data from the National
Institutes of Health, received over $379 million in NIH research
funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and
700 students, the School of Medicine is recognized worldwide for its
superior education and training of the next generation of physician-
scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three
hospitals — its flagship hospital, the Hospital of the University of
Pennsylvania, rated one of the nation's "Honor Roll" hospitals by
U.S.News & World Report; Pennsylvania Hospital, the nation's first
hospital; and Penn Presbyterian Medical Center — a faculty practice
plan; a primary-care provider network; two multispecialty satellite
facilities; and home care and hospice.
Public release date: 17-Jun-2008
Contact: Karen Kreeger
karen.kreeger@
215-349-5658
University of Pennsylvania School of Medicine
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
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http://www.CNSfoundation.org/
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http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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