Topical fluoxetine as a novel therapeutic that improves wound healing in diabetic mice

Chuong Minh Nguyen, Danielle Tartar, Michelle Dawn Bagood, Michelle So, Alan Vu Nguyen, Anthony Gallegos, Daniel Fregoso, Jorge Serrano, Duc Nguyen, Doniz Degovics, Andrew Adams, Benjamin Harouni, Jaime Joel Fuentes, Melanie Gareau, Robert William Crawford, Athena Soulika, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

Abstract

Diabetic foot ulcers represent a significant source of morbidity in the U.S., with rapidly escalating costs to the health care system. Multiple pathophysiological disturbances converge to result in delayed epithelialization and persistent inflammation. Serotonin (5-hydroxytryptamine [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 nonhealing 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 toward 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.

Original languageEnglish (US)
Pages (from-to)1499-1507
Number of pages9
JournalDiabetes
Volume68
Issue number7
DOIs
StatePublished - Jan 1 2019

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Fluoxetine
Wound Healing
Serotonin
Diabetic Foot
Aptitude
Wounds and Injuries
Serotonin Uptake Inhibitors
Therapeutics
Keratinocytes
Inflammation
Morbidity
Delivery of Health Care
Phenotype
Costs and Cost Analysis
Skin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Topical fluoxetine as a novel therapeutic that improves wound healing in diabetic mice. / Nguyen, Chuong Minh; Tartar, Danielle; Bagood, Michelle Dawn; So, Michelle; Nguyen, Alan Vu; Gallegos, Anthony; Fregoso, Daniel; Serrano, Jorge; Nguyen, Duc; Degovics, Doniz; Adams, Andrew; Harouni, Benjamin; Fuentes, Jaime Joel; Gareau, Melanie; Crawford, Robert William; Soulika, Athena; Isseroff, Roslyn Rivkah.

In: Diabetes, Vol. 68, No. 7, 01.01.2019, p. 1499-1507.

Research output: Contribution to journalArticle

Nguyen, CM, Tartar, D, Bagood, MD, So, M, Nguyen, AV, Gallegos, A, Fregoso, D, Serrano, J, Nguyen, D, Degovics, D, Adams, A, Harouni, B, Fuentes, JJ, Gareau, M, Crawford, RW, Soulika, A & Isseroff, RR 2019, 'Topical fluoxetine as a novel therapeutic that improves wound healing in diabetic mice', Diabetes, vol. 68, no. 7, pp. 1499-1507. https://doi.org/10.2337/db18-1146
Nguyen, Chuong Minh ; Tartar, Danielle ; Bagood, Michelle Dawn ; So, Michelle ; Nguyen, Alan Vu ; Gallegos, Anthony ; Fregoso, Daniel ; Serrano, Jorge ; Nguyen, Duc ; Degovics, Doniz ; Adams, Andrew ; Harouni, Benjamin ; Fuentes, Jaime Joel ; Gareau, Melanie ; Crawford, Robert William ; Soulika, Athena ; Isseroff, Roslyn Rivkah. / Topical fluoxetine as a novel therapeutic that improves wound healing in diabetic mice. In: Diabetes. 2019 ; Vol. 68, No. 7. pp. 1499-1507.
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