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Diabetes. 2019 May 2. pii: db181146. doi: 10.2337/db18-1146. [Epub ahead of print]

Topical Fluoxetine as a Novel Therapeutic that Improves Wound Healing in Diabetic Mice.

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Department of Dermatology, University of California - Davis.
Dermatology Section, VA Northern California Health Care System.
Department of Biological Sciences, California State University, Sacramento.
Department of Anatomy, Physiology and Cell Biology, University of California - Davis.
Shriners Hospital for Children, Northern California, Sacramento.
Department of Dermatology, University of California - Davis


Diabetic foot ulcers (DFU) represent a significant source of morbidity in the United States with rapidly escalating costs to the healthcare system. Multiple pathophysiological disturbances converge to result in delayed epithelialization and persistent inflammation. Serotonin (5-HT) and the selective serotonin reuptake inhibitor, fluoxetine (FLX) have both been shown to have immunomodulatory effects. Here we extend their utility as a therapeutic alternative for non-healing diabetic wounds by demonstrating their ability to interact with multiple pathways involved in wound healing. We show that topically applied FLX improves cutaneous wound healing in vivo Mechanistically, we demonstrate that FLX not only increases keratinocyte migration but also shifts the local immune milieu towards a less inflammatory phenotype in vivo without altering behavior. By targeting the serotonin pathway in wound healing, we demonstrate the potential of repurposing FLX as a safe topical for the challenging clinical problem of diabetic wounds.


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