| Zhao Wenyue,Li Na,Li Kejun,et al.Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis[J].Chinese Journal of Radiological Medicine and Protection,2022,42(11):830-838 |
| Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis |
| Received:August 23, 2022 |
| DOI：10.3760/cma.j.cn112271-20220823-00341 |
| KeyWords:Radiation-induced pulmonary fibrosis Cellular senescence Stem cell therapy Gingival mesenchymal stem cells |
| FundProject:国家自然科学基金(32071241,31971168);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-042) |
| Author Name | Affiliation | E-mail | | Zhao Wenyue | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | | | Li Na | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | | | Li Kejun | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | | | Wang Yan | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | | | He Ningning | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | | | Du Liqing | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | duliqing@irm-cams.ac.cn | | Liu Qiang | Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China | |
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| Abstract:: |
| Objective To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% (t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) (t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% (t=21.83,P<0.05), and inhibited the expressions of SASP (t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation.Conclusions GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF. |
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