Origin of Scar-Forming Cells in Kidney Fibrosis Identified - Brigham and Women's Hospital
New research identifies the precursors of the scar forming cells that play a major role in progressive kidney fibrosis.
Boston, MA, February 16, 2010 --(PR.com)-- Chronic kidney disease has reached epidemic proportions in the US, affecting as many as 16 million sufferers. A common underlying characteristic in many diseases, progressive fibrosis can lead to organ failure and death in progressive kidney disease. New research from Brigham and Women’s Hospital (BWH) has identified the precursors of the scar forming cells called myofibroblasts. These findings appear online on January 1, in American Journal of Pathology.
“Development of new therapies for kidney diseases has been slow in part because our lack of understanding of the mechanism of the disease,” said corresponding author Jeremy Duffield, MD, PhD, assistant professor of medicine in the Renal Division at BWH. Pericytes, undifferentiated connective tissue cells in blood vessels, have only recently been described in the kidney, but this study has identified these cells as a major source of scar forming myofibroblasts, which contribute to fibrosis in the kidney.
The researchers used genetic manipulation to develop mice that express protein labels exclusively and permanently in renal tubular epithelial cells. They then induced injury in the kidney and, by looking for labeled cells, were able to determine whether any tubular cells had moved into the interstitium or had acquired the ability to behave as myofibroblasts. Contrary to current wisdom in two separate models of human diseases, they did not detect any epithelial cells contributing to the scar forming cells. Next the authors developed mice that express protein labels exclusively in perivascular cells of the capillaries of the kidneys known as pericytes and found that these cells are the precursor of myofibroblasts.
The study not only reverses the currently accepted models for the development of fibrosis in the kidney, but raises the possibility that pericyte migration from the capillaries in response to kidney injury, directly leads to the loss of microvasculature in the kidney. “By targeting the cellular interaction between pericytes and endothelial cells we hope to develop new therapies that target both fibrosis progression and loss of microvasculature,” added Dr. Duffield.
The study was funded by NIH, NIDDK, ARRA Stimulus Challenge Grant, American Society of Nephrology, Harvard Stem Cell Institute and National Science Council, Taiwan.
About Brigham and Women's Hospital:-
Brigham and Women's Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. In July of 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit http://www.brighamandwomens.org/
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“Development of new therapies for kidney diseases has been slow in part because our lack of understanding of the mechanism of the disease,” said corresponding author Jeremy Duffield, MD, PhD, assistant professor of medicine in the Renal Division at BWH. Pericytes, undifferentiated connective tissue cells in blood vessels, have only recently been described in the kidney, but this study has identified these cells as a major source of scar forming myofibroblasts, which contribute to fibrosis in the kidney.
The researchers used genetic manipulation to develop mice that express protein labels exclusively and permanently in renal tubular epithelial cells. They then induced injury in the kidney and, by looking for labeled cells, were able to determine whether any tubular cells had moved into the interstitium or had acquired the ability to behave as myofibroblasts. Contrary to current wisdom in two separate models of human diseases, they did not detect any epithelial cells contributing to the scar forming cells. Next the authors developed mice that express protein labels exclusively in perivascular cells of the capillaries of the kidneys known as pericytes and found that these cells are the precursor of myofibroblasts.
The study not only reverses the currently accepted models for the development of fibrosis in the kidney, but raises the possibility that pericyte migration from the capillaries in response to kidney injury, directly leads to the loss of microvasculature in the kidney. “By targeting the cellular interaction between pericytes and endothelial cells we hope to develop new therapies that target both fibrosis progression and loss of microvasculature,” added Dr. Duffield.
The study was funded by NIH, NIDDK, ARRA Stimulus Challenge Grant, American Society of Nephrology, Harvard Stem Cell Institute and National Science Council, Taiwan.
About Brigham and Women's Hospital:-
Brigham and Women's Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. In July of 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit http://www.brighamandwomens.org/
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Suzanne Benz
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http://www.brighamandwomens.org/
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Boston, MA 02115 USA
Suzanne Benz
(617) 534-1604
http://www.brighamandwomens.org/
75 Francis Street
Boston, MA 02115 USA
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