(Press-News.org) Researchers from Brigham and Women's Hospital (BWH) have identified what they believe to be the cells responsible for fibrosis, the buildup of scar tissue. Fibrotic diseases, such as chronic kidney disease and failure, lung disease, heart failure and cirrhosis of the liver, are estimated to be responsible for up to 45 percent of deaths in the developed world.
The findings are published online in the journal Cell Stem Cell.
"Previous research indicated that myofibroblasts are the cells responsible for fibrosis," said Benjamin Humphreys, MD, PhD, senior author of the research paper and a physician scientist in the Renal Division at BWH. "But there was controversy around the origin of this cell. Identifying the origin could lead to targeted therapies for these very common diseases."
With the knowledge that fibrosis appears to radiate from blood vessels, Humphreys and colleagues examined the hedgehog signaling pathway, which normally regulates organ development but whose roles in the adult are less clear. They noticed that in adult mice, a hedgehog pathway gene called Gli1 was specifically expressed in a rare group of cells located around blood vessels in all solid organs. This pattern suggested that the cells might play a role in fibrosis. To test this hypothesis the researchers tagged this protein in tissue with varying forms of fibrosis, and found that these cells proliferated by almost 20-fold under chronic injury and turned into myofibroblasts.
"We believe that this cell population is responsible for about 60 percent of all organ myofibroblasts," said Humphreys.
After identifying these cells, first author Rafael Kramann, MD, Humphreys and colleagues set out to determine whether removing these cells would lead to improvement in organ function.
Using a genetic strategy in mice, the researchers were able to ablate these Gli1 cells, while leaving other cells unharmed. In mice with kidney and cardiac fibrosis, the ablation of these cells resulted in reduction in fibrosis and rescued heart function.
"We've found that these Gli1 progenitor cells differentiate into myofibroblasts, and in fibrotic disease, when they are ablated, we can rescue organs and organ function," said Humphreys.
Researchers note that the genetic strategy employed in the preclinical model is not feasible in humans. For this reason, future research involves the exploration of drugs that could specifically target and shut off these fibrosis-causing stem cells with the hope that either an existing drug or a new drug could translate to a potential therapy for humans.
Humphreys also notes that this cell population plays a role in the aging process. "Most organs develop fibrosis as we age," he said. "Specifically, in the kidney we lose one percent of kidney function as a result of fibrosis for each year that we age. We look forward to future research, using human tissue, to confirm our findings in humans and work to develop a potential therapy."
INFORMATION:
This research was supported by the Harvard Stem Cell Institute, the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Deutsche Forschungsgemeinschaft.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. 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, resources and to follow us on social media, please visit BWH's online newsroom.
New research from North Carolina State University and the University of Minnesota shows that the majority of consumers will accept the presence of nanotechnology or genetic modification (GM) technology in foods - but only if the technology enhances the nutrition or improves the safety of the food.
"In general, people are willing to pay more to avoid GM or nanotech in foods, and people were more averse to GM tech than to nanotech," says Dr. Jennifer Kuzma, senior author of a paper on the research and co-director of the Genetic Engineering in Society Center at NC State. ...
Bethesda, MD (Dec. 2, 2014) -- Women with celiac disease present with fertility problems no more often than women in the general population, according to a new study in Gastroenterology1, the official journal of the American Gastroenterological Association.
"Despite inconsistent findings from small studies, concern has been raised that celiac disease may cause infertility," said lead study author Nafeesa N. Dhalwani, PhD, from the University of Nottingham, United Kingdom. "Celiac patients should rest assured; our findings indicate that women with celiac disease do not ...
A research team from Kiel University (CAU) and Goethe University Frankfurt has jointly created a synthetic surface on which the adhesion of E. coli bacteria can be controlled. The layer, which is only approximately four nanometres thick, imitates the saccharide coating (glycocalyx) of cells onto which the bacteria adhere such as during an infection. This docking process can be switched on and off using light. This means that the scientists have now made an important step towards understanding the relationship between sugar (carbohydrates) and bacterial infections. Their ...
This news release is available in German.
The FK506-binding protein 51 (FKBP51) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the very similar functional counterplayer FKBP52. Scientists at the Max Planck Institute of Psychiatry in Munich have now developed the first potent and highly selective inhibitor of FKBP51. The so-called SAFit-ligand inhibits FKBP51 enhancing growth of neuronal cell cultures and improving ...
Molecular clocks -- based on changes in genetic material -- indicate much younger ages for a wide variety of plants found as fossils in southern Argentina than do the solid, geologic dates of those fossils, according to geoscientists who surveyed recent paleobotanical discoveries in Patagonia.
The finding suggests serious biases in molecular clocks, which are heavily used to date many kinds of living things. It also directly refutes a widely-held idea about how most Southern Hemisphere plant and animal groups attained their current distributions.
Geologists date fossils ...
A team of scientists has revealed how certain harmful bacteria drill into our cells to kill them. Their study shows how bacterial 'nanodrills' assemble themselves on the outer surfaces of our cells, and includes the first movie of how they then punch holes in the cells' outer membranes. The research, published today in the journal eLife, supports the development of new drugs that target this mechanism, which is implicated in serious diseases. The team brings together researchers from UCL, Birkbeck, University of London, the University of Leicester, and Monash University ...
In the city that never sleeps, it's easy to overlook the insects underfoot. But that doesn't mean they're not working hard. A new study from North Carolina State University shows that insects and other arthropods play a significant role in disposing of garbage on the streets of Manhattan.
"We calculate that the arthropods on medians down the Broadway/West St. corridor alone could consume more than 2,100 pounds of discarded junk food, the equivalent of 60,000 hot dogs, every year - assuming they take a break in the winter," says Dr. Elsa Youngsteadt, a research associate ...
ARLINGTON HEIGHTS, Ill. (December 2, 2014) - If you are one of the millions of Americans who experiences a severe allergic reaction to food, latex or an insect sting, you should know the first line of defense in combating the reaction is epinephrine. Unfortunately, not all medical personnel know how important epinephrine is in bringing an allergic reaction under control.
According to new guidelines published in the Annals of Allergy, Asthma and Immunology, the scientific publication of the American College of Allergy, Asthma and Immunology (ACAAI), the fast administration ...
AUSTIN, Texas -- Researchers at The University of Texas at Austin have identified a network of genes that appear to work together in determining alcohol dependence. The findings, which could lead to future treatments and therapies for alcoholics and possibly help doctors screen for alcoholism, are being published this week in the journal Molecular Psychiatry.
By comparing patterns of genetic code from the brain tissue of alcoholics and nonalcoholics, the researchers discovered a particular set of genes co-expressed together in the individuals who had consumed the most ...
CHICAGO - According to a new long-term study, diabetic patients with even mild coronary artery disease face the same relative risk for a heart attack or other major adverse heart events as diabetics with serious single-vessel obstructive disease. Results of the study were presented today at the annual meeting of the Radiological Society of North America (RSNA).
Researchers at the University of British Columbia and St. Paul's Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, ...
