| Xu Ying,Hu Wentao,Zhou Guangming.The malignant transformation of bystander lung epithelial cells induced by proton irradiation simulating space radiation[J].Chinese Journal of Radiological Medicine and Protection,2025,45(4):282-289 |
| The malignant transformation of bystander lung epithelial cells induced by proton irradiation simulating space radiation |
| Received:September 18, 2024 |
| DOI：10.3760/cma.j.cn112271-20240918-00355 |
| KeyWords:Space radiation TGF-β1 Proton radiation Bystander cell β-arrestin1 Malignant transformation |
| FundProject:国家自然科学基金(32071243) |
| Author Name | Affiliation | E-mail | | Xu Ying | School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College of Soochow University, Suzhou 215123, China | | | Hu Wentao | School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College of Soochow University, Suzhou 215123, China | wthu@suda.edu.cn | | Zhou Guangming | School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College of Soochow University, Suzhou 215123, China | |
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| Abstract:: |
| Objective To investigate the influence of TGF-β1 on the malignant transformation of bystander cells after proton irradiation simulating space radiation, and its underlying mechanism. Methods Normal human bronchial epithelial cells BEAS-2B were exposed to proton irradiation at 0, 0.2, 0.5, and 1.0 Gy to simulate space radiation. Supernatants from cell culture media were collected as a conditioned medium (CM) for treating bystander BEAS-2B cells. The enzyme-linked immunosorbent assay (ELISA) was employed to detect TGF-β1 levels within the CM. The soft agar colony formation assay was performed to assess the rate of malignant transformation of bystander cells. Immunofluorescence and Western blot techniques were utilized to examine the localization of β-arrestin1 in CM-treated bystander cells, with or without the TGF-β1 receptor inhibitor SB525334. The malignant transformation of bystander cells was assessed via soft agar colony formation assay under CM treatment, combined with either a TGF-β1 receptor inhibitor or β-arrestin1 knockdown. Additionally, mRNA and protein levels of epithelial-mesenchymal transition(EMT)-related genes (e.g., E-cadherin, N-cadherin, Fibronectin1, and Vimentin) were analyzed through qRT-PCR and Western blot, respectively. Results Contrasting with the 0 Gy group, the proton irradiation groups exhibited a dose-dependent increase in TGF-β1 secretion after 24 h (t=3.38, 8.32, 10.96, P<0.05), and a corresponding rise in the soft agar colony formation rate of CM-treated bystander cells (t=5.04, 7.20, 10.78, P<0.05). Immunofluorescence and Western blot results indicated that with escalating doses, CM-treated bystander cells showed increased β-arrestin1 into nuclei (t=7.57, 7.51, P<0.05), being stimulated by TGF-β1 and inhibited by SB525334. The SB525334 application or β-arrestin1 knockdown significantly inhibited the malignant transformation and EMT induced by proton irradiation in bystander cells. This inhibition further reduced the soft agar colony formation rate (t=2.84, 3.39, P<0.05), and increased mRNA and protein levels of the E-cadherin gene in CM-treated bystander cells exposed to 1 Gy proton irradiation (t=7.33, 5.38, P<0.05) while reducing the mRNA and protein levels of N-cadherin, Fibronectin1, and Vimentin genes (t=4.37, 4.10, 5.29, 10.65, 5.15, 3.11, P<0.05). Conclusions Proton irradiation simulating space radiation can enhance TGF-β1 secretion from lung epithelial cells, inducing β-arrestin1 into nuclei in bystander cells, thereby spurring the malignant transformation of cells. The TGF-β1/β-arrestin1 pathway plays a crucial role in this process. |
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