Dynamics of wound healing signaling as a potential therapeutic target for radiation‐induced tissue damage

Abstract

We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury.

Effect of mesenchymal stem cells and platelet-derived growth factor on the healing of radiation induced ulcer in rats

“…Improvement of wound healing by application of PDGF to radiation-damaged tissue was not observed in this study. Radiation exerts a negative effect on the mitogenic potential of PDGF [46]; thus, the normal function of PDGF could have been impaired in irradiated skin. Early treatment of radiation-induced skin ulceration can lessen pain and reduce secondary infection and damage of adjacent tissues.…”

Superoxide Dismutase Mimic, MnTE-2-PyP Enhances Rectal Anastomotic Strength in Rats after Preoperative Chemoradiotherapy

“…Some studies have shown that CRT can increase tissue reactive oxygen species (ROS), leading to excessive oxidative stress, tissue destruction, and even toxicity [9,27,28]. We deduced that excessive ROS and oxidative stress may be one of the reasons for the increased AL after preoperative CRT.…”

“…It has been reported that radiation can generate free radicals or reactive oxygen species (ROS), leading to oxidative stress [8]. The ROS generated by ionizing radiation and excessive oxidative stress can initiate DNA and non-DNA damage, oxidize lipids and proteins, and even cause tissue damage [9,10]. Additionally, the generation of ROS and their by-products was considered to mediate the cytotoxic effects of chemotherapy, which may lead to cell damage [11].…”

Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma

“…105 The pharmacological functions of the major listed HDAC inhibitors are summarized in Table 2. [106][107][108][109][110][111][112][113][114][115] Vorinostat, the first FDAapproved HDAC inhibitor, was approved for the treatment of cutaneous T-cell lymphoma (CTCL). Vorinostat belongs to the hydroxamic acid class of inhibitors, and its targets include class I, II, and IV HDACs.…”