PVT1 is associated with proteins responsible for reduced blood
filtration
PHOENIX, Ariz. - April 22, 2011 - A gene called PVT1 may help
reduce the kidneys ability to filter blood, leading to kidney
disease, kidney failure and death, according to a study published
today by researchers at the Translational Genomics Research
Institute (TGen).
The TGen team found PVT1 expression levels increased up to 5-fold
in response to hyperglycemia, or high blood sugar, a condition that
often accompanies diabetes.
But by knocking down or reducing the expression of the PVT1gene,
TGen researchers lowered the amount of proteins associated with the
excessive accumulation of extracellular matrix (ECM) in glomeruli,
part of the basic filtration unit of kidneys, according to the TGen
study published today in the online scientific journal Public
Library of Science (PLoS) ONE.
The accumulation of excessive ECM within the mesangial cells, which
regulate blood flow in capillaries inside the kidney, is a hallmark
of diabetic nephropathy, or kidney disease, which is the leading
cause of reduced life expectancy among the nation's growing numbers
of diabetics.
"The goal of this study was to identify possible molecular
mechanisms by which PVT1 may contribute to the development and
progression of diabetic nephropathy in mesangial cells," said Dr.
Johanna DiStefano, the study's senior author and Director of TGen's
Diabetes, Cardiovascular and Metabolic Diseases Center.
"Despite the growing magnitude of the disease, the molecular
mechanisms underlying the etiology of diabetic nephropathy remain
poorly understood," Dr. DiStefano said.
PVT1, also known as plasmacytoma variant translocation 1, was
previously identified by Dr. DiStefano's team as a candidate gene
for End Stage Renal Disease (ESRD), or kidney failure. Too much
PVT1 also has been associated with breast and ovarian cancers, in
which it may help cause cells to multiply out of control and fail
to go through the normal process of cellular death.
Through RNA interference, which helps control which genes are
active and the degree of their activity, researchers reduced the
expression of PVT1, which in turn reduced the protein levels of ECM
components.
In a related finding, TGen scientists discovered that PVT1 affects
the expression of other genes - FN1, COL4A1 and PAI-1 - in a manner
that is at least partially independent of TFFB1, a gene associated
with tissue fibrosis, or tissue damage.
"Delineation of the relationship between TGFB1 and PVT1 represents
a critical component toward understanding the molecular mechanisms
underlying the regulation of ECM in diabetic nephropathy," said Dr.
Lucrecia Alvarez, the study's lead author and a TGen post-doctoral
fellow.
Funding for the study was provided, in part, by the American
Diabetes Association.
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About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]