Researchers Identify Possible Treatment and Diagnostic Targets for Diabetic Foot Ulcers

Diabetic foot ulcers are one of the major complications of type 2 diabetes, with very limited treatment options. Now a group of researchers at the University of Miami Miller School of Medicine has identified major new mechanisms that not only play an important role in the inhibition of the wound healing, but also point to a new direction for therapeutic and diagnostic development.

In an elegant NIH-funded study using laser-captured microdissection and complex genomics approaches, as well as multiple models including patients' tissue samples, acute human and porcine wound models, the researchers demonstrated that the bacterium Staphylococcus aureus, a frequent colonizer of diabetic foot ulcers, inhibits wound closure and induces a microRNA known as miR-15b-5p to suppress certain inflammatory- and DNA repair-related genes. This mechanism of inhibiting healing in diabetic foot ulcers was previously unknown.

"These novel findings introduce a few new concepts and may have high clinical relevance," says Marjana Tomic-Canic, PhD, a professor of dermatology, vice chair of research, and director of the wound healing and regenerative medicine research pProgram in the department of dermatology and cutaneous surgery, who was the lead researcher in the study. "We identified suppression of DNA damage repair as a novel contributor to pathophysiology of diabetic foot ulcers and confirmed the functional consequence—accumulation of DNA fragments—as one of their unique features. In addition, contrary to current belief and approaches to decreasing inflammation in diabetic foot ulcers, perhaps a robust, timed, and controlled stimulation of inflammatory response may reactivate acute healing and trigger healing cascade. These newly identified molecular mechanism provide new treatment and diagnostic strategies for patients."

The research findings were reported in an article, "Staphylococcus Aureus Triggers Induction of miR-15b-5p to Diminish DNA Repair and De-Regulate Inflammatory Response in Diabetic Foot Ulcers," published by the Journal of Investigative Dermatology, with Tomic-Canic as senior author. Departmental coinvestigators were Robert S. Kirsner, MD, PhD, Harvey Blank Professor and Chair; Irena Pastar, PhD, a research assistant professor; and Stephen C. Davis, BS, a research professor.

"To the best of our knowledge this is one of the first in-depth studies revealing the complexity of the underlying molecular mechanisms responsible for pathophysiology of diabetic foot ulcers that shows interplay of wound bacteria, miRNAs and cellular behaviors," Tomic-Canic says. "The lack of critical information about their molecular pathology has been preventing the development of new and effective treatment strategies. We believe the results of this study, in addition to advancing the understanding of molecular mechanisms that contribute to inhibition of healing in patients, also identify novel targets for biomarker and therapeutic development for the growing population of diabetic patients affected with chronic ulcers."

Source: Miller School of Medicine