The skin is the largest organ of the human body. It protects against environmental influences and pathogens, regulates body temperature, and protects the body against dehydration. In humans, the skin renews itself completely approximately every month by constantly shedding the dead cells on the skin surface and replacing them with new cells which have moved up from the basal layer of the epidermis. When the skin is injured, this process is accelerated in order to facilitate rapid wound closure to keep germs from penetrating inside the body.
Researchers of the Max Delbrόck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now been able to show that the signal molecule, c-Met, which regulates cell growth and cell migration during embryonic development, also plays a key role in wound healing in the skin. If c-Met is missing in the skin cells, no new tissue can form and close the wound. The paper of Jolanta Chmielowiec, PhD student of Professor Walter Birchmeier, and Professor Carmen Birchmeier has been published in the Journal of Cell Biology (Vol.177, Nr. 1, pp. 151 – 162, 2007).
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.
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