Protein May Play Important Role in Diabetic Wound Healing

In a recent study, investigators found that the application of a topical gel that contains the gene heat shock protein 60 significantly increased wound healing in a mouse model of diabetes.

The heat shock protein 60 (Hsp60) is now known to be released at the injury site and is involved with tissue regeneration and healing. These findings may be important for creating treatments for wound healing and scar reduction, especially for patients with diabetes, according to the study published by npj Regenerative Medicine.

The fungal communities in these wounds are known to cause bacterial-fungal biofilms, which prevent healing. Millions of patients with diabetes develop a diabetic wound in their lifetime, and many require amputation, which can cost the health care system billions of dollars per year.

These ulcers are commonly formed on the bottom on the foot due to reduced sensation, poor circulation, skin irritation, and other factors. Increased insight into genetics about wound healing could lead to improved treatments.

“This study proposes an unusual role for a well-known gene,” said senior study author Shawn Burgess, PhD. “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 Hsp60 are known to prevent protein misfolding, and has been shown to be a signaling molecule that initiates inflammatory response.

“A major problem is that diabetes inhibits wound healing,” Dr Burgess said. “The patients frequently get foot ulcers that never heal.”

Previous findings indicated that the protein is critical for the inflammatory response, so the investigators believed that it may also be involved in regeneration.

In the study, researchers used zebrafish with Hsp60 removed from the genome. This is an excellent model to test this theory, since zebrafish are able to regenerate various tissues, including fins. Knock out fish developed normally without the protein, but were unable to regenerate their cells and fins when the investigators injured the cells involved with hearing or amputating a caudal fin, respectively, according to the study.

The investigators then used floursecently tagged leukocytes, immune cells, and discovered that there was a reduced number of leukocytes at the injury site in the Hsp60 knock out fish. This finding suggests that the protein promoted inflammation for wound healing.

“When we injected Hsp60 directly to the site of injury, the tissue surrounding the wound started to regenerate faster,” Dr Burgess said. “That’s when we got really excited.”

The investigators then tested this finding in mice, and found that applying a topical treatment of Hsp60 to a wound in mice models of diabetes resulted in complete healing within 21 days. Mice that did not receive the treatment did not heal as rapidly, according to the study.

“We hope that topical treatment with Hsp60 will act the same way in humans,” Dr Burgess said. “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?”

The investigators are also testing other heat shock proteins to determine if any others are involved in healing. Since the mechanisms behind cell signaling in wound healing are still largely unknown, these findings also highlight the need for more basic research.

“When we understand the biology better, we can more easily apply it to human treatments,” Dr. Burgess concluded.