For scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, what seemed like a disappointing result turned out to be an important discovery.
Their findings, published online this week in the journal Proceedings of the National Academy of Sciences (PNAS), provide conclusive proof that, when a muscle is injured, white blood cells called macrophages play a crucial role in its regeneration. The scientists also uncovered the genetic switch that controls this process, a finding that opens the door for new therapeutic approaches not only to sports injuries but also to diseases such as Duchenne muscular dystrophy.
Normally, macrophages – the white blood cells known for engulfing and eliminating bacteria and other infectious agents – are drawn to areas of injury. Once there, they act as garbage men, eliminating the dead cells and releasing pro-inflammatory factors, fending off infection. After clearing up the debris, macrophages stop releasing those pro-inflammatory factors, and start making anti-inflammatory factors that promote repair in the damaged area. This shift from clearing debris to promoting building is known as macrophage polarization, and Claus Nerlov, Nadia Rosenthal and colleagues proved that it is essential for muscles to regenerate properly.
“There seems to be this point of no return”, says Rosenthal: “if macrophages don’t make this switch, then the muscle won’t repair itself – you just end up with scar, instead of new tissue”.
Nerlov and his research group at EMBL were studying a protein called C/EBPâ, whose production increases in response to inflammation. They had genetically engineered mice in which this boost in C/EBPâ production was blocked, to see what effect this had on the development of the different cells involved in the immune system. To their dismay, the answer appeared to be ‘almost none’. The modified mice developed normally, and had normal blood cells – except their macrophages didn’t polarize. Although this result fell short of the scientists’ expectations of understanding how blood cells develop, it raised an interesting possibility in the context of Rosenthal’s research into muscle regeneration. If these mice could not repair muscle injuries properly, it would prove that macrophage polarization is indispensable for muscle regeneration. The two groups teamed up to investigate how the ability to respond to muscle injury was affected in mice whose C/EBPâ production boost had been blocked. Their findings proved that macrophages still migrated to the injured site and cleared the debris, but because they failed to make that all-important switch, the muscle didn’t repair properly, becoming scarred instead.
At a stroke, the EMBL scientists confirmed the importance of macrophages in repairing muscle tissue and discovered its genetic basis. Normally, inflammatory factors trigger an increase in C/EBPâ production, which in turn activates genes that cause the macrophage to polarize.
“From a medical point of view, it would seem that the trick to improve muscle repair is finding a way to increase C/EBPâ production and keep it high”, Nerlov concludes, adding “if we can now figure out exactly which key genes C/EBPâ controls, that will give us even more potential targets.”
As well as investigating the other steps on this molecular pathway, the scientists are currently studying a possible role for macrophage polarization in repairing heart muscle, with a view to better understanding and treating heart disease.Source Article
Lena Raditsch | EMBL
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy