Rosiglitazone And Deferoxamine Combination Mitigates Radiation-induced Skin Fibrosis And Promotes Dermal Adipogenesis And Fat Browning
Year: 2026
Type: conference-paper
Abstract: PURPOSE: Radiation-induced skin fibrosis is a significant pathology that impacts wound healing, oncologic treatment timing, and patient quality of life. However, few targeted therapies are available to prevent or mitigate its progress. Radiation-induced fibrosis is characterized by chronic inflammation, hypovascularity, hypocellularity, and dysregulated collagen deposition. Previously, deferoxamine (DFO), an iron chelator, has been shown to rescue radiation-induced fibrosis via HIF-1a upregulation and ferroptosis inhibition, resulting in angiogenesis and reduced oxidative stress. Likewise, rosiglitazone has been demonstrated to mitigate fibrosis and promote adipogenesis in irradiated skin. In an animal model, we demonstrate that rosiglitazone and DFO combination therapy is superior to monotherapy in mitigating radiation-induced skin fibrosis. METHODS: Four groups of five 6-8-week-old C57BL/6J mice received 30 grays of dorsal radiation in six fractionated doses. After six weeks to allow for radiation-induced skin fibrosis to develop, each group received two weeks of every-other-day subcutaneous injections of 0.5 mg rosiglitazone + 3 mg DFO (combination, 0.5 mg rosiglitazone only, 3 mg DFO only, or vehicle control. Subsequently, dorsal skin was harvested, paraffin-embedded, and sectioned for histology and immunofluorescence staining. RESULTS: Combination therapy, rosiglitazone, and DFO each demonstrated decreased dermal collagen density on Massons trichrome compared to vehicle (72.6% combination vs 75.6% DFO vs 83.5% rosiglitazone vs 84.8% control). Combination therapy significantly increased dermal fat thickness (dermal fat thickness / total skin thickness = 55.2% combination vs 42.2% DFO vs 50.0% rosiglitazone vs 43.1% control) and increased dermal brown fat composition (dermal fat UCP1-positive area = 6.92% combination vs 1.06% DFO vs 5.78% rosiglitazone vs 0.90% control). DFO and combination therapy both demonstrated increased CD31 density vs control (1.66% combination vs 2.87% DFO vs 1.28% rosiglitazone vs 1.55% control). CONCLUSION: Rosiglitazone and DFO combination therapy reduced skin fibrosis, increased dermal fat thickness, and induced dermal fat browning in an animal model of radiation-induced skin fibrosis. This supports prior evidence that inducing dermal adipose tissue thickening and browning plays a regenerative role in wound healing and fibrosis-prevention. However, adipocytes, especially brown adipocytes, have high metabolic demands and are highly susceptible to reactive oxygen species and hypovascularity that persist following radiation injury. We hypothesize that DFO-induced angiogenesis and reactive oxygen species mitigation supports adipogenesis and dermal fat browning by rosiglitazone; collectively, these regenerative factors mitigate radiation-induced fibrosis. Future studies aim to further investigate these mechanisms and their clinical applications.© 2026. Plastic Surgery Research Council | All rights reserved |*Source: https://ps-rc.org/meeting/Program/2026/106.cgi*
Institutions: Stanford University, Brigham and Women's Hospital
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160618682
FWCI:
Cites:
Cited by:
Related to: