The excessive activity of repair cells in the early stages of tissue recovery sets the stage for fibrosis by priming the activation of an important growth factor, according to a study in The Journal of Cell Biology.
Myofibroblasts are highly contractile cells that repair damaged tissues by replacing and reorganizing the extracellular matrix (ECM), the meshwork that fills the space around cells, in order to draw a wound closed.
When myofibroblasts are not properly regulated, however, they continue to act on healed tissues and produce excessive amounts of ECM. Excessive ECM production is involved in conditions such as fibrosis, the development of damaging scar tissue in organs.
Transforming growth factor β1 (TGF-β1) is a key signaling molecule within the ECM that promotes tissue fibrosis. Boris Hinz and colleagues previously found that myofibroblasts pull on inactive TGF-β1 complexes to release the active form of the signaling molecule from the ECM.
The University of Toronto researchers then wanted to find out whether the structural changes that myofibroblasts make in the ECM during wound healing might also make it easier for the ECM to release activated growth factor later in the process.
The researchers found that wounds containing increased numbers of myofibroblasts exhibited much higher levels of ECM organization, with components arranged into long, thin fibers. Hinz and colleagues then devised a series of experiments to test how this highly organized ECM configuration affects TGF-β1 activation.
They found that higher levels of organization and tension in the ECM always resulted in high amounts of activated TGF-β1 being released by the contractile force of myofibroblasts.
Their results indicate that, over time, as myofibroblasts remodel and stiffen the ECM during wound healing, the matrix becomes a loaded "mechanical spring" that puts strain on TGF-β1 complexes, causing them to be easily pulled apart and activated by contracting myofibroblasts.
Because TGF-β1 induces further myofibroblast activity and, ultimately, tissue fibrosis, limiting ECM reorganization during wound healing might therefore be an effective therapeutic approach to prevent fibrosis.
Klingberg, F., et al. 2014. J. Cell Biol. doi:10.1083/jcb.201402006
About The Journal of Cell Biology
The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works, and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jcb.org.
Research reported in the press release was supported by the Canadian Institutes of Health Research, the Collaborative Health Research Program, the Canada Foundation for Innovation and Ontario Research Fund, the Heart and Stroke Foundation Ontario, and the European Union's Seventh Framework Program.
Rita Sullivan King | Eurek Alert!
Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo
Full of hot air and proud of it
18.04.2018 | University of Pittsburgh
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.
“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Power and Electrical Engineering
19.04.2018 | Life Sciences
18.04.2018 | Materials Sciences