Heat Shock Protein Hsp60 Involved in Regeneration and Wound Healing
Heat shock proteins are involved in the cellular response to stresses, including heat, hence the name. They assist in protein quality control and correct function, one important part of the larger panoply of cellular maintenance activities. Here, researchers find that the heat shock protein Hsp60 also influences the role that the immune system plays in wound healing, and can be used to spur greater regeneration:
Researchers have identified a novel role for a gene known as heat shock protein 60 (Hsp60), finding that it is critical in tissue regeneration and wound healing. The study found that topical treatment of an Hsp60-containing gel dramatically accelerates wound closure in a diabetic mouse model. The study also describes the mechanism by which this works, finding that Hsp60 protein is released at the site of injury, signaling wound healing to initiate. The findings may help in the development of effective therapeutics for accelerating wound closure in diabetic patients, as well as for normal wound healing and scar reduction. "This study proposes an unusual role for a well-known gene. 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."
Protein products of the Hsp60 gene are known primarily for their role in ensuring that other proteins are folded correctly. The Hsp60 protein has also been reported to serve as a signaling molecule that induces an inflammatory response to bacterial infection from a cut. Based on previous findings that the Hsp60 protein was necessary for an inflammatory response, the researchers hypothesized that the molecule might also be involved in an organisms' ability to regenerate. Using zebrafish - an ideal model for this work because fish can regenerate many tissues, including fins - the researchers used targeted mutagenesis, making specific and intentional changes to the DNA sequence of a gene, to "knock out" Hsp60 from the genome. The mutant fish appeared to develop normally, but when the researchers wounded them by injuring the cells involved in hearing or amputating a caudal fin, the fish were unable to regenerate their cells and fins, respectively. Using fluorescently tagged leukocytes (immune cells that flock to the site of injury as part of the inflammatory response under normal conditions), the researchers demonstrated that without the Hsp60 gene, there were significantly reduced numbers of leukocytes at the injury site. This suggested that the Hsp60 protein was somehow acting as an attractant that promoted inflammation, a necessary component of wound healing. "When we injected Hsp60 directly to the site of injury, the tissue surrounding the wound started to regenerate faster. That's when we got really excited."
However, the most striking finding from the study was that actually applying a topical treatment of the Hsp60 protein to a puncture wound in diabetic mice stimulated complete healing after only 21 days. Mice without the treatment did not show improvement over the same time frame. Although promising, this finding has only been shown in mice and is yet to be tested in humans. "We hope that topical treatment with Hsp60 will act the same way in humans. And we believe it will, but more work is needed. We also want to know if it will help any wound heal, not just wounds encountered by people with diabetes. Will it reduce scarring and increase the speed of healing?"