Dataset Information

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

ABSTRACT: The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post-recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS-detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

SUBMITTER: Lavin CV

PROVIDER: S-EPMC8572785 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

Lavin Christopher V CV Abbas Darren B DB Fahy Evan J EJ Lee Daniel K DK Griffin Michelle M Diaz Deleon Nestor M NM Mascharak Shamik S Chen Kellen K Momeni Arash A Gurtner Geoffrey C GC Longaker Michael T MT Wan Derrick C DC

Journal of cellular and molecular medicine 20211006 21

The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) ...[more]

PMID: 34612609

Similar Datasets

Project description:BackgroundBoth TGFβ and estradiol (E2), a form of estrogen, are pro-fibrotic in the skin. In the connective tissue disease, systemic sclerosis (SSc), both TGFβ and E2 are likely pathogenic. Yet the regulation of TGFβ in E2-induced dermal fibrosis remains ill-defined. Elucidating those regulatory mechanisms will improve the understanding of fibrotic disease pathogenesis and set the stage for developing potential therapeutics. Using E2-stimulated primary human dermal fibroblasts in vitro and human skin tissue ex vivo, we identified the important regulatory proteins for TGFβ and investigated the extracellular matrix (ECM) components that are directly stimulated by E2-induced TGFβ signaling.MethodsWe used primary human dermal fibroblasts in vitro and human skin tissue ex vivo stimulated with E2 or vehicle (ethanol) to measure TGFβ1 and TGFβ2 levels using quantitative PCR (qPCR). To identify the necessary cell signaling proteins in E2-induced TGFβ1 and TGFβ2 transcription, human dermal fibroblasts were pre-treated with an inhibitor of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, U0126. Finally, human skin tissue ex vivo was pre-treated with SB-431542, a TGFβ receptor inhibitor, and ICI 182,780, an estrogen receptor α (ERα) inhibitor, to establish the effects of TGFβ and ERα signaling on E2-induced collagen 22A1 (Col22A1) transcription.ResultsWe found that expression of TGFβ1, TGFβ2, and Col22A1, a TGFβ-responsive gene, is induced in response to E2 stimulation. Mechanistically, Col22A1 induction was blocked by SB-431542 and ICI 182,780 despite E2 stimulation. Additionally, inhibiting E2-induced ERK/MAPK activation and early growth response 1 (EGR1) transcription prevents the E2-induced increase in TGFβ1 and TGFβ2 transcription and translation.ConclusionsWe conclude that E2-induced dermal fibrosis occurs in part through induction of TGFβ1, 2, and Col22A1, which is regulated through EGR1 and the MAPK pathway. Thus, blocking estrogen signaling and/or production may be a novel therapeutic option in pro-fibrotic diseases.

Dataset Information

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

Publications

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets