A protein-folding gene helps heal wounds

Zebrafish can regenerate fins and many other types of body tissues, making them an ideal model system to study tissue regeneration. Kazakovmaksim/iStock/Thinkstock

Wound healing after an injury is a precise, highly controlled process. Complex mechanisms are rapidly summoned to trigger an inflammatory response, close the wound, and then restore the tissue. Humans have a limited ability to restore certain tissues compared to non-mammalian vertebrates, such as zebrafish.          

Zebrafish can regenerate multiple body tissues, including fins. They can also fully recover hearing loss by replacing dead hair cells—the tiny sensory cells in ears. This restorative ability helps makes zebrafish an ideal model to study tissue regeneration. In a study led by Dr. Shawn Burgess of NIH’s National Human Genome Research Institute (NHGRI), researchers screened for genes that are essential for hair cell regeneration in zebrafish. The results were published in npj Regenerative Medicine on October 27, 2016.

The scientists identified the heat shock protein 60 gene, Hsp60, as an important player in tissue regeneration. They showed that genetically modified zebrafish lacking Hsp60 failed to regenerate hair cells or fins after an injury.

The Hsp60 protein, also called Hspd1, is known for its ability to facilitate proper protein folding. Previous research had also shown that Hsp60 is necessary for an inflammatory response. The current study uncovers a new function of this protein as a mediator of wound healing. Experiments measuring immune responses suggested that Hsp60 attracts immune cells towards the site of injury and triggers signaling involved in wound closure. Injecting Hsp60 at an injury site in zebrafish accelerated tissue regeneration, the researchers showed.

The scientists also investigated the tissue-regenerating effects of Hsp60 in diabetic mice. Diabetes is known to impair wound healing in both mice and humans—for instance, leading to foot ulcers that don’t heal in people. The researchers topically applied a gel containing Hsp60 to the diabetic mice to treat a skin puncture wound. Upon Hsp60 application, the diabetic mice showed nearly complete wound healing within 21 days. In diabetic mice without the Hsp60 treatment, the wounds remained unhealed.

These findings demonstrate the importance of HSP60 in triggering tissue regeneration. The researchers are now working to test other heat shock proteins to see if they are also involved in wound healing. Future studies will seek to determine whether the benefits seen in diabetic mice could be achieved on human wounds.

“This study proposes an unusual role for a well-known gene,” Burgess says. “This gene is found in every organism from bacteria to man. We have shown that in vertebrates, it has a surprising role in immunity that is essential for wound healing.”