IPF fills the delicate gas exchange region of the lung with scar tissue, progressively restricting breathing. The Duke University Medical Center researchers have discovered that some commonly held ideas about the origins of the scar-forming (fibrotic) cells are oversimplified, if not wrong.
“We are the first to show that pericytes, a population of cells previously described to play a role in the development of fibrosis in other organs, are present in fibrotic lung tissue,” said Christina Barkauskas, M.D., a pulmonary fellow in the Duke Division of Pulmonary, Allergy and Critical Care Medicine.
The team found that pericytes move from blood vessels into fibrotic regions, and were in the damaged lungs of both humans and mice. In mice, they also showed that the epithelial cells, which make up the lacy sacs called alveoli, could divide and repair the damage in the gas-exchange location, but these cells were not the source of scarring.
Idiopathic pulmonary fibrosis affects about 100,000 people in the U.S. each year and leads to death within three years of diagnosis.
The study was published the week of Nov. 28 in PNAS Plus online edition.
“We don’t know yet whether the pericytes make the scar matrix itself or just release signals that stimulate the scarring process, but either way, they are a potential target for new therapies,” said Brigid Hogan, Ph.D., senior author and chair of the Duke Department of Cell Biology.
The researchers used genetic lineage tracing to study the origin of cells that gathered in fibrotic areas. They gave several different cell types an indelible fluorescent tag and then followed the cells over time.
The cells kept the tag even if they multiplied, migrated within the lung, or differentiated into another cell type.
Paul Noble, M.D., co-author and chief of the Pulmonary Division at Duke, said that identifying the source of the lethal expansion of the scarring (fibroblast) cells is a critical missing link in understanding disease progression.
Previous studies had suggested that the epithelial cells in the alveoli are a source of fibroblast accumulation after lung injury, he said.
“This study used the newest tracing approaches to conclusively demonstrate, however, that the alveolar epithelium isn’t a significant source for fibroblast accumulation following lung injury in mice,” Noble said. “The studies suggest that there may be several sources for the scar-forming cell accumulation in fibrosis, including pericytes, which hadn’t been implicated in lung fibrosis until now.”
Noble said that the study data provide new insights into the sources of scar-forming cells and would help to target the correct cell population that causes disease progression.
Now the researchers are focusing on what these cells may make that could promote a healing process. “One idea is that perhaps in IPF these epithelial cells have lost the ability to repair damage to the lung, so that scarring continues inexorably and cannot be restrained – perhaps we could find a way to assist the repair process,” Hogan said. “Promoting the healing process might be another therapeutic approach.”
Other authors include Jason R. Rock and Yan Xue of the Duke Department of Cell Biology; Michael J. Cronce and Jiurong Liang of the Duke Division of Pulmonary, Allergy and Critical Care Medicine; and Jeffrey R. Harris of the Duke Division of Cellular Therapy. Jason Rock is now with the University of California -- San Francisco.
Mary Jane Gore | EurekAlert!
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy