Dr. Poss is excited at the prospect that "there may indeed be microRNAs that when manipulated appropriately could impact and even increase the ability of a damaged human organ to regenerate healthy tissue."

Regeneration, the replacement of damaged or lost body parts, is a shared trait among some animal species “ as any youngster who has cut an earthworm in half can attest to. But the repair of damaged tissue and organs in higher animals is also one of the primary goals of current stem cell research.

The common aquarium pet, zebrafish, is an excellent genetic model system, capable of regenerating its spinal cord, retina, heart and fins. First author, Viravuth Yin, and his colleagues focused on fin regeneration, as it entails the coordination of a large number of different cells types to recreate the functional organ.

The scientists noted that many microRNAs were differentially regulated during fin regeneration, but that the expression of one microRNA in particular “ miR-133 “ showed an antagonistic relationship with fin regeneration: When miR-133 levels are high, fin regeneration is inhibited; When miR-133 levels are low, fin regeneration is promoted.

miR-133 is regulated by the FGF signaling pathway, so by tweaking FGF activity, Dr. Poss and colleagues were able to manipulate miR-133 levels. The researchers found that experimentally increasing miR-133 levels slowed regeneration, while decreasing miR-133 levels enhanced regeneration.

The finding that microRNA levels are being controlled during appendage regeneration to assist changes in gene expression makes sense, given how important these RNAs are in developmental biology. We were surprised, though, to see that modulating the amount of a single microRNA family could influence regenerative success in zebrafish, explains Dr. Poss.

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The researchers say that these findings could lead scientists to ways of preventing the bone destruction that is associated with some diseases. There is the potential to control inflammation and also to control bone destruction. This interferon response is very effective at preventing the destruction of bones, which is one of the major issues with rheumatoid arthritis, said Dr. Ivashkiv. So, what it does is sets up the next series of studies, in animal models, to try to determine whether this induction of interferon is beneficial or not.

The new research could also help explain how a patient involved in a University of Pennsylvania gene therapy experiment that used an adenovirus to deliver the gene died. Host response to adenoviral vectors is dependant on both IRF1 and TNF.

What we have described is that TNF has both pathogenic affects ”it helps to sustain some of these inflammatory chemokines, but it also has a potential protective effect, because some of these interferon responses limit the amount of cell proliferation and they can also help to limit inflammation.

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