Researchers Identify Molecule That Induces Wound Healing (4/20/2007)

After injury, even adult muscles can heal very well because they have a reserve supply of muscle stem cells, called satellite cells, which they can utilize for repair. Until now, it was unclear how this supply of satellite and muscle progenitor cells, out of which both muscle cells as well as satellite cells develop, keeps itself “fresh”. Developmental biologists Professor Carmen Birchmeier, Dr. Elena Vasyutina, and Diana Lenhard of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now demonstrated that a molecular switch, abbreviated RBP-J, regulates this “fountain of youth”.

If the switch is absent, the satellite cells generate muscle cells in an uncontrolled way, resulting in the depletion of the satellite cell reserves. As a consequence, too few muscles form during the developmental phase of a living organism and the fetus can no longer build up a reserve supply of satellite cells. The MDC scientists’ research report, which could be of significance for the future development of stem cell therapies, has just been published in the online edition of the Proceedings of the National Academy of Sciences (PNAS)*.

When the skin is injured, it first scabs over as a first aid measure, so-to-speak, sealing the wound to keep germs out. Starting from the edge of the wound, keratinocytes then migrate across the wound. They proliferate especially quickly, thereby rapidly forming new skin tissue which covers the wound in a short time. This very fast growing tissue, the hyperproliferative epithelium, also fills up the wound with new skin cells so that finally new tissue is formed which replaces the scab.

The signal molecule, c-Met, regulates this migration process from the edge of the wound. It is a receptor molecule also localized on epithelial cell membranes. The role c-Met plays in developmental biology has been studied intensively during the past years by Professor Carmen Birchmeier and her research team. Interacting with c-Met is a growth factor given the name hepatocyte growth factor/scatter factor (HGF/SF) because it was discovered to be a growth factor in liver cells (hepatocytes). The liver is an organ that regenerates especially quickly after injury. In cancer research, this factor also plays a key role as scatter factor, which Professor Walter Birchmeier and his colleagues were repeatedly able to demonstrate.

The duo HGF/SF and c-Met is crucial in regulating cell migration. Together, the two are not only released in the liver, but also in the lung, the kidneys, and the heart when these organs are injured. As MDC researchers were now able to show, this is also the case with skin wounds: HGF/SF and c-Met are increasingly released by the hyperproliferative skin tissue. Hence, this tissue promotes its own growth. However, while c-Met is normally found in both the skin and the hair follicles (and in wounds is increasingly released in the hyperproliferative epithelium), HGF/SF is proven to be present prior to injury in the hair follicles but not in the skin. HGF/SF is not active in the skin until after an injury at which time it is particularly active at the wound edges of the hyperproliferative epithelium.

With a special technique, the MDC researchers specifically deactivated the gene for c-Met in mice. They discovered that mice whose skin cells no longer produce c-Met do not form new skin when the skin is injured. In mice that still have some skin cells with active c-Met, because these cells escaped the genetic mutation, wound healing is not blocked. However, it starts later and takes twice as long as in the normal case. That means that only skin cells with active c-Met can build up fast-growing, protective new tissue to close a skin wound.

*c-Met is essential for wound healing in the skin

Note: This story has been adapted from a news release issued by the Max Delbrück Center for Molecular Medicine

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