(WHS-P2.03) Radiation Triggers An Early Scarring Response Involving Epithelial-Mesenchymal Transition And Upregulation Of Pro-Fibrotic Genes In A Human Ex Vivo Skin Model
Friday, May 17, 2024
10:30 AM – 11:30 AM East Coast USA Time
Radiation-induced skin fibrosis (RISF) is a severe consequence of cutaneous injury following irradiation, producing functional impairment and reduced quality of life for patients. Epithelial-mesenchymal transition (EMT) plays a global role in fibrosis by pathologically sustaining extracellular matrix production after tissue injury. To elucidate the early cutaneous response to radiation, a human ex vivo skin model was developed. Skin from human subjects (n=7) was irradiated at a dose of 3.5Gy, maintained at an air-liquid interface, and collected over a 15-day period. Tissue fibrosis was captured by measurement of dermal collagen bundles in histologic sections using automated quantitative assessment. Dermal collagen thickness increased following radiation, supporting evolving fibrosis in this model. Radiation treatment also triggered the induction of fibrosis-associated genes actin alpha 2 smooth muscle (ACTA2), collagen alpha-1 chain (COL1A1), connective tissue growth factor (CTGF), and fibronectin 1 (FN1). In addition, an EMT-like response was detected via immunohistochemical analysis of irradiated skin, which demonstrated decreased E-cadherin and increased vimentin levels in comparison to non-irradiated controls. In conclusion, a scarring response involving global processes of fibrosis was successfully induced in human skin ex vivo, providing a platform for further study of molecular and cellular events underlying RISF and leading to the development of targeted therapies for early intervention.