The study at Boston Children's Hospital also found that Lin28A promotes tissue repair in part by enhancing metabolism in mitochondria, suggesting that a mundane cellular "housekeeping" function could open new avenues for developing regenerative treatments. (Agencies)
"Efforts to improve wound healing and tissue repair have mostly failed, but altering metabolism provides a new strategy which we hope will prove successful," said the study's senior investigator George Q Daley director of Boston Children's Stem Cell Transplantation Programme.
"The enhanced metabolic rate we saw when we reactivated Lin28A is typical of embryos during their rapid growth phase," added Shyh-Chang Ng, co-first author on the paper with Hao Zhu, both scientists in the Daley Lab.
To better understand how Lin28a promotes tissue repair, the researchers systematically looked at what specific RNAs it binds to. They initially had their sights on a tiny RNA called Let-7, which is known to promote cell maturation and ageing.
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 are showing the converse - that enhancement of mitochondrial metabolism can boost tissue repair and regeneration, recapturing the remarkable repair capacity of juvenile animals," said Shyh-Chang.
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 Lin28A itself is difficult to introduce into cells, the fact that we were able to activate mitochondrial metabolism pharmacologically gives us hope," Shyh-Chang said.
Lin28A didn't universally induce regeneration in all tissues. Heart tissue showed little effect, and while the researchers were able to enhance the re-growth of finger tips in newborn mice, they could not in adults.
The study at Boston Children's Hospital also found that Lin28A promotes tissue repair in part by enhancing metabolism in mitochondria, suggesting that a mundane cellular "housekeeping" function could open new avenues for developing regenerative treatments.