Penn Researchers
Identify Gene that Regulates Development of Heart Cells
January / February 2003
Scientists at the University of Pennsylvania School of Medicine
have identified and described a small gene that regulates
the delicate balance involved in the healthy growth and replication
of heart muscle cells.
"This finding is likely to be important for our understanding
of the causes of congenital heart disease. It is also relevant
to our attempts to regrow damaged heart muscle," said the
senior author of the study,
Jonathan A. Epstein, MD, of Penn's Departments of Medicine,
and Cell and Developmental Biology. The study appeared in
the September 20, 2002 issue of the journal Cell.
The newly identified heart gene, Hop (an acronym for homeodomain
only protein), is a small protein that lacks certain residues
required for DNA binding, but is activated early in fetal
development and continues modulating the expression of cardiac
specific genes throughout life. Hop appears to bind directly
to another important regulator of development, serum response
factor (SRF), and block SRF from binding to DNA.
By inhibiting the expression of SRF, Hop protects cardiac
muscle cells from over development, therefore preventing fatal
abnormalities. Congenital heart defects are the most common
congenital defect and occur in one out of every 125 births.
"There has been a lot of effort to try to determine how SRF
is regulated in different tissues," adds Dr. Epstein. "Now
we see that Hop plays a vital part."
All previous proteins and genes of this family function by
regulating other genes, binding to DNA and turning on the
expression of other genes. "Although this gene has the same
structure and is very similar in sequence to other transcription
factors or master regulators, it doesn't bind to DNA and directly
regulates expression of lots of other genes," says Dr. Epstein.
"To the basic science community, this is a surprising and
novel finding."
At Penn, the researcher's next step is to understand how
this gene is working in the adult heart. "Currently, we
understand very little about what regulates how a heart
muscle cell
works
in the adult. The Hop gene is particularly interesting because
it may be relevant to understanding heart failure in adults,"
adds Dr. Epstein.
Unlike many other cells in the body, once a heart muscle
cell stops dividing, usually around the time of birth, it
is almost always permanent. Because Hop is binding to SRF,
it may help to regulate how a heart muscle cell decides when
to stop dividing and when to start growing as a mature muscle
cell.
Scientists know it is possible for a heart muscle cell to
divide and work at the same time because this happens in the
heart cells of an embryo and a newborn infant. New research
is focused on determining how to make heart muscle cells divide
again. In the future, through medication or gene therapy scientists
hope to regrow heart muscle cells that have been damaged during
a heart attack.
The study was funded by the National Institutes of Health,
the American Heart Association, and the W. W. Smith Foundation.
Others who participated in the research were from the Victor
Chang Cardiac Research Institute, Carlinghurst, Australia,
Baylor College of Medicine, Houston, TX, and the Chang Institute
and the University of New South Wales, Australia.
|
|
Referring Physicians: To speak with a Penn physician
or refer a patient, contact PennHealth through the secure online
referral form or by calling
1-800-789-PENN
(7366). |
 |
|
|
|
