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Control of the Mineralocorticoid Receptor with Spironolactone Enhances Wound Healing and Mitigates Fibrosis of Burn Wounds
Fuat Baris Bengur, MD; Shawn J. Loder, MD; W. Vincent Nerone, BA; David Guerrero, BS; Thomas Mitts, MD; Aleksander Hinek, PhD; Lauren Kokai, PhD; J Peter Rubin, MD
University of Pittsburgh
2022-01-15
Presenter: Fuat Baris Bengur, MD
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: J Peter Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background
Adhesion, contracture, and the formation of disfiguring, hypertrophic scars remain as one of the most recalcitrant problems in care of the burned patient. The central pathology driving fibrosis is an imbalance of the extracellular matrix (ECM). The mineralocorticoid receptor (MR) is a nuclear receptor with shared ligand-activity from both its primary activator, aldosterone, and glucocorticoids and has cell specific effects on ECM production in fibroblasts and keratinocytes. Here we demonstrate that MR-inhibition with FDA-approved spironolactone enhances epithelialization healing and mitigates hypertrophic collagen deposition after burns in mice.
Methods
Female athymic mice sustained bilateral 1 cm full-thickness thermal injury and were stratified into either a) vehicle, b) spironolactone, c) aldosterone, or d) aldosterone and spironolactone. Aldosterone was applied via subcutaneous pump (Alzet) and spironolactone was delivered intraperitoneally. Mice followed photographically for 4-to-6-weeks. At sacrifice wound biopsies were collected for H&E, Trichrome, Pentachrome and proteomic analysis.
Results
Histologic evaluation of healing wounds from burned mice demonstrated persistence of inflammation, wound edema, and immature ECM. In mice treated with spironolactone, this effect is alleviated by 4-weeks post-injury concurrent with gross findings of rapid wound epithelialization. Spironolactone treatment also enhanced gross and histologic evidence of scar resolution and resulted in a decrease in collagen staining versus controls.
Conclusions
We found a significant early improvement in wound epithelialization with spironolactone therapy. This suggests a potentially distinct effect from the proposed ECM-modifying strategy hypothesized. More analysis is needed but this data supports that MR-inhibition may be a valuable new therapeutic in treatment of burn scars.
