London, Mar 3 : Researchers at Rockefeller University conducted a series of experiments in mice and discovered a small RNA molecule that helps exposed skin cells protect the body from bacteria, dehydration and even cancer by forming a tough cellular protective barrier.
30,000 of our outermost skin cells die per minute and that is when new cells travel from the inner layer of the skin to its surface to form this protective barrier.
The findings of this study, led by Rui Yi, a postdoc who works with Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development, not only provide a new insight into the evolution of skin, but also propose how healthy cells can turn cancerous.
Yi said that hundreds of these tiny RNA molecules, called microRNAs, are expressed in skin, "but there was something curious about one in particular, microRNA-203. As an embryo develops, the expression of microRNA-203 jumps very quickly over just two days. From being barely detectable at day 13, this microRNA becomes the most abundant expressed in skin."
MicroRNAs regulate genes outside of the cell's nucleus and were discovered in mammals in 2001.
Yi along with Fuchs, who is also a Howard Hughes Medical Institute investigator and Rebecca C. Lancefield Professor at Rockefeller, discovered that mouse skin is mainly consists of undifferentiated stem cells on the 13th day of development. After 2 days, these stem cells were observed to leave the inner layer of the skin to start differentiating into cells of the outermost, protective layer. This was the time when MicroRNA-203's expression shot up indicating its crucial role in the barrier's development.
The researchers discovered that this microRNA was located only in very specific types of skin, called the stratified epithelial tissues, and that too in this skin type's outer layers. Besides, this expression pattern is quite similar to vertebrates like humans, zebrafish, chickens etc.
"If it has been expressed in this very specific tissue for a long time and across several species, it means that it probably plays an important role there," said Yi.
In the 1st set of experiments Yi used a genetic technique for early expression of microRNA in the inner layer of the skin, where stem cells propagate at a high speed. Later, in 2nd set of experiments, he used an antagomir, a molecule that binds directly to microRNA-203 and ceases its ability to carry out its function, to block microRNA-203 from functioning in the outer layer.
While in the first set, he discovered that the propagation of stem cells was considerably less than the time when microRNA-203 wasn't expressed, thereby leading to the formation of very thin skin in mice. The researchers observed that the stem cells were not able to proliferate. This was not because microRNA-203 destroyed them but because it curbed the activity of a molecule known as p63 that is responsible for keeping cells, primarily stem cells, proliferating.
On the other hand, Yi discovered that in the 2nd set of experiments, the outer layer cells significantly proliferated, much more than they did during microRNA-203's expression. This was due to the absence of microRNA-203 to shut down p63's functions.
"We found that microRNA-203 acts to stop the translation of the p63 protein. The result is a swift transition from proliferating stem cells within the innermost layer of the epidermis and terminally differentiating cells as they exit this layer and move outward to the skin surface," Nature quoted Fuchs, as saying.
The results of this study may have important implications in cancer, as p63 is excessively found in cancer cells.
"As a next step, we are going to examine whether low expression of microRNA-203 is associated with squamous cell carcinomas and whether by putting back microRNA-203 we can inhibit the growth of these cancer cells," said Fuchs.
The study is recently published in Nature.