"We were confident that Let-7 would be the mechanism," says Shyh-Chang. "But there was something else involved."
Specifically, the researchers found that Lin28a also enhances the production of metabolic enzymes in mitochondria, the structures that produce energy for the cell. By revving up a cell's bioenergetics, they found, Lin28a helps generate the energy needed to stimulate and grow new tissues.
"We already know that accumulated defects in mitochondrial metabolism can lead to aging in many cells and tissues," says Shyh-Chang. "We are showing the conversethat enhancement of mitochondrial metabolism can boost tissue repair and regeneration, recapturing the remarkable repair capacity of juvenile animals."
Further experiments showed that bypassing Lin28a and directly activating mitochondrial metabolism with a small-molecule compound also had the effect of enhancing wound healing. This suggests the possibility of inducing regeneration and promoting tissue repair with drugs.
"Since Lin28 itself is difficult to introduce into cells, the fact that we were able to activate mitochondrial metabolism pharmacologically gives us hope," Shyh-Chang says.
Lin28A didn't universally induce regeneration in all tissues. Heart tissue showed little effect, and while the researchers were able to enhance the regrowth of finger tips in newborn mice, they could not in adults.
"Lin28a could be a key factor in constituting a healing cocktail," says Shyh-Chang, "but there are other embryonic factors that remain to be found."
|Contact: Irene Sege|
Boston Children's Hospital