Bulk RNA molecules rejuvenate skin, say researchers

Do you want to smooth out your wrinkles, erase scars and sunspots, and look younger years? Millions of Americans are turning each year to lasers and prescription drugs to rejuvenate their skin, but the way this rejuvenation works has never been fully explained. Researchers at Johns Hopkins have discovered that laser treatments and retinoic acid medications share a common molecular process. In addition, this pathway – which allows skin cells to detect bulk RNA molecules – is also detected in mice when they regenerate hair follicles. The results are described in the June 26 issue of Nature Communications.

"Understanding the biology behind how cell damage can lead to this type of regeneration can harness a new generation of therapeutics," says Luis Garza, MD, Ph.D., associate professor of dermatology at the Faculty of Medicine at the University of Ottawa. Johns Hopkins University.

Researchers have known for decades that mice, unlike humans, can regenerate hair follicles after a deep wound. Recent studies by Garza and other researchers have shown that bulk RNA fragments, called self-encoding double-stranded RNAs (dsRNAs), can stimulate this regeneration. They hypothesize that this could be due to the fact that dsRNAs are released by damaged cells at the site of a wound. Garza and his colleagues were curious about whether dsRNAs also played a role in skin rejuvenation treatments such as laser therapy, microneedling and facial abrasion, all of which cause temporary damage to the cells of the skin. skin. Although these treatments are well established among dermatologists, the researchers did not understand why they were working.

The team took biopsies from 17 patients treated at Johns Hopkins Hospital with conventional laser skin rejuvenation to electrically erase sunspots and wrinkles. All patients were Caucasian women aged 55 and over, and treatments were performed on the face and arms. Skin biopsies were collected prior to laser treatment and one week after the procedure.

Garza and his colleagues analyzed gene expression levels in each sample and found that the genes involved in the detection of dsRNAs as well as those involved in the production of the skin's natural retinoic acid were all expressed at higher levels after laser treatment. Next, the researchers treated isolated human skin cells with a loose dsRNA, mimicking the effect of laser treatment. The amount of retinoic acid in the cells has more than tenfold. Commercially produced retinoic acid is already used to treat acne, wrinkles and sunspots.

"It's no coincidence that laser rejuvenation and retinoic acid have been effective treatments against premature aging of the skin, caused by the sun and other forms of exposure," Garza said. "They are actually working in the same molecular ways and nobody knew it until now."

To further strengthen and understand the connection, the researchers turned to mice. They knew that in mice and humans, a protein called receptor 3 (TLR3) detects dsRNAs. When Garza's group developed mice lacking TLR3, animals could no longer regenerate hair follicles after injury. But when the researchers administered retinoic acid to these mice, they regained the ability to regenerate the follicles. The results indicate a pathway involving TLR3 that detects double-stranded RNA and activates the synthesis of retinoic acid.

"In hindsight, that makes a lot of sense because retinoic acid is already a pillar of wrinkle reduction and nobody knew what had activated it," Garza says. "We now know that the damage leads to a dsRNA, which leads to the activation of TLR3 and to the synthesis of retinoic acid."

The results could lead to new strategies to reduce wrinkles and sunspots by innovatively combining retinoic acid and laser treatments, says Garza. And they could also lead to ways to regenerate hair follicles, as do mice when there is an increase in sRNA after an injury.

"After a burn, humans do not regenerate structures such as the hair follicles and sweat glands that were there," says Garza. "It is possible, in the light of these new findings, that double-stranded RNA can improve the appearance of burn scars."