Cell-type-specific radiosensitivity in the human parotid gland and its implications for radiotherapy-induced dysfunction

초록

Background: The human parotid gland, vital for oral health and digestion, comprises mainly acinar and ductal cells, each with unique responses to environmental stimuli such as radiation. Understanding the differential effects of radiation on these cells is crucial for therapeutic advancements in treating radiation-induced salivary gland damage. Methods: Acinar and ductal cells were isolated from human parotid glands and cultured in both 2D and 3D environments. Morphology, proliferation capacity, and transepithelial electrical resistance (TER) were assessed to characterize each cell type. To evaluate radiosensitivity, both cell types were exposed to 5 Gy of irradiation, and post-radiation cellular responses were compared. Differential gene expressions were analyzed under normal and irradiated conditions using microarray analysis. Selected genes were further validated using qRT-PCR and immunohistochemistry (IHC) to confirm cell-type-specific expression patterns and radiation-induced change. Results: Acinar cells exhibited strong epithelial junctional features, including high E-cadherin and ZO-2 expression, and showed higher TER values than ductal cells. After irradiation, acinar cells demonstrated sustained proliferation loss and activation of inflammatory pathways, such as IL-17 and MAPK signaling. In contrast, ductal cells displayed early growth reduction followed by stabilization and showed increased expression of ECM- and repair-related genes, including GREM1, HAS2, SNAIL1, and CEMIP. Radiation-induced transcriptional responses were distinctly cell-type specific. Conclusion: Acinar and ductal cells exhibit fundamentally different structural properties and radiation responses. Acinar cells appear more vulnerable to inflammation-associated injury, whereas ductal cells activate adaptive remodeling pathways. These findings support the development of cell-type-specific strategies to protect acinar cells and enhance ductal-mediated repair during radiotherapy.

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