The Role of FABP5 in Radiation-Induced Human Skin Fibrosis

Abstract

Radiation-induced skin fibrosis is a detrimental and chronic disorder that occurs after radiation exposure. The molecular changes underlying the pathogenesis of radiation-induced fibrosis of human skin have not been extensively reported. Technical advances in proteomics have enabled exploration of the biomarkers and molecular pathogenesis of radiation-induced skin fibrosis, with the potential to broaden our understanding of this disease. In this study, we compared protein expression in radiation-induced fibrotic human skin and adjacent normal tissues using iTRAQ-based proteomics technology. We identified 186 preferentially expressed proteins (53 upregulated and 133 downregulated) between radiogenic fibrotic and normal skin tissues. The differentially expressed proteins included keratins (KRT5, KRT6A, KRT16 and KRT17), caspase-14, fatty acid-binding protein 5 (FABP5), SLC2A14 and resistin. Through bioinformatic analysis of the proximal promoters, common motifs and corresponding transcriptional factors were identified that associate with the dysregulated proteins, including PAX5, TBX1, CLOCK and AP2D. In particular, FABP5 (2.15-fold increase in fibrotic skin tissues), a transporter of hydrophobic fatty acids, was investigated in greater detail. Immunohistochemistry confirmed that the protein level of FABP5 was increased in fibrotic human skin tissues, especially in the epidermis. Overexpression of FABP5 resulted in nuclear translocation of SMAD2 and significant activation of the profibrotic TGF-β signaling pathway in human fibroblast WS1 cells. Moreover, exogenous FABP5 (FABP5-EGFP) could be incorporated by skin cells and intensify TGF-β signaling, indicating a communication between the microenvironment and skin fibrosis. Taken together, our findings illustrate the molecular changes during radiation-induced human skin fibrosis and the critical role of FABP5 in activating the TGF-β signaling pathway.

Plasma Proteins as Biomarkers of Mortality After Total Body Irradiation in Mice

“…Some of these proteins (IL-6 and SAA) were previously reported as biomarkers for radiation biodosimetry 9 and are related to radiation-induced hematopoietic response events or acute-phase responses. In contrast, the others (IL-22, IL-1a, IGFBP5, and RETN) were reported to be altered in response to radiation [19][20][21][22] or to be involved in radiationinduced pulmonary fibrosis (FSTL1) 23 or CNS damage (PLAU). 24 Although the roles of most of these proteins in radiation injury are unclear, our study provides preliminary evidence indicating that these biomarkers are associated with survival or mortality upon radiation exposure; however, further verification is warranted.…”

Genome-Wide Analysis Reveals Zinc Transporter ZIP9 Regulated by DNA Methylation Promotes Radiation-Induced Skin Fibrosis via the TGF-β Signaling Pathway

“…Human skin samples were obtained from a victim of an iridium radiation accident as reported previously (Song et al, 2018). The fibrotic skin samples were obtained 160 days after irradiation from the right limb, which was exposed to an iridium-192 metal chain (with an activity of 966.4 GBq or 26.1 Ci).…”

X-ray induces mechanical and heat allodynia in mouse via TRPA1 and TRPV1 activation

“…Skin injury is another common side effect after radiation treatment. 6,7 Radiation may cause variety of physical skin reactions and contributes to pain, itch, and burning. 8 A moderate-to-severe skin reaction occurs in about 85% of patients treated with radiotherapy.…”