Proteomic analysis of the pathogenesis of radiation-induced skin fibrosis

Recently, Suzhou University and panomic cooperated to analyze the protein of rat skin fibrosis using the platform of label free proteomics The cooperative article is entitled: targeting the ubiquitin protein system, published in International Journal of radiation oncology, biology, Physics, the influencing factor is 4.258 Radiotherapy is an important part of the treatment plan for cancer patients However, ionizing radiation may obviously damage skin tissue and seriously weaken its function Radioactive materials released from nuclear accidents, wars and other sources have been a threat to induced skin damage The forms of skin chronic radiation injury include skin atrophy, hyperplasia and irreversible fibrosis The cellular mechanism of radiation-induced fibrosis is a multicellular process involving the interaction of various cell systems in skin tissue Radiation-induced skin fiber is a chronic disorder after radiation The pathogenesis of this skin fibrosis includes fibrocyte variation, deposition of collagen and accessory structures, vascular damage and immune disorders Many studies have shown that the fibrotic phenotype of fibroblasts is stimulated by many levels of cytokines, including transforming growth factor - β (TGF - β), tumor necrosis factor - α (TNF - α), interleukin-4 (IL-4), interleukin-1 β (IL-1 β) In addition, it can also change the downstream signal pathway of TGF - β, especially increase the expression of phosphorylated Smad transcription factors In addition to the above cytokines, few people know the key molecules and pathways involved in radiation-induced skin fibrosis No effective treatment has developed to completely inhibit the fibrosis process Therefore, understanding the regulatory network, signal cascade and metabolic pathway in the process of radiation-induced skin fibrosis can contribute to the development of toxic therapeutic drugs For the discovery of high-throughput proteins, proteomics analysis is one of the most common application strategies, and proteomics network analysis is becoming a key tool to understand molecular networks The changes of differentially expressed proteins in radiation-induced skin fibrosis have not been reported In this study, the researchers established a rat model of radiation-induced skin fibrosis and studied its proteomic profile and possible strategies The researchers selected rats with 30 or 45 Gy electron beam radiation Label free protein quantitative method was used to qualitatively and quantitatively evaluate the protein expression of skin fibrosis and adjacent normal tissues in rats Human skin cells HaCaT and WS-1 were irradiated by X-ray The activity of protease was obtained by fluorescence probe The effect of protease inhibitor on TGF - β signal was determined by WB and immunofluorescence The efficacy of bortezomib in rat skin wound healing was used to evaluate the degree of skin injury The researchers found that radiation induced abnormal growth in the epidermis and dermis of rats and humans 196 preferentially expressed and 80 unique proteins were identified in irradiated fibrotic skin Through bioinformatics analysis, ubiquitin proteasome has obvious ploidy change and has been studied in more detail In vitro experiments, the researchers found that radiation can lead to the gradual decline of proteasome activity in human skin cells The proteasome inhibitor bortezomib inhibited the down stream signal of TGF - β, but not the secretion of TGF - β In addition, bortezomib improved radiation-induced injury and weakened epidermal hyperplasia The results show that the molecular mechanism changes during radiation-induced skin fibrosis, and the ubiquitin protease complex system will be an effective strategy (BIOON Com)