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
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News