二氧化硅诱导的肺纤维化与衰老、Fgr 以及骨髓单核细胞/巨噬细胞的募集有关。
Silica Induced Lung Fibrosis Is Associated With Senescence, Fgr, and Recruitment of Bone Marrow Monocyte/Macrophages.
机构信息
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, U.S.A.
出版信息
In Vivo. 2021 Nov-Dec;35(6):3053-3066. doi: 10.21873/invivo.12601.
BACKGROUND/AIM: The role of senescence and bone marrow-derived cells in silica-induced pulmonary fibrosis is unknown.
MATERIALS AND METHODS
C57BL/6HNsd, p16, and tdTOMp16+ mice were intratracheally injected with 200 mg/kg crystalline silica or irradiated (20 Gy) to the thoracic cavity and followed for the development of lung fibrosis.
RESULTS
The p16 mice demonstrated senescence by day 7 after silica exposure. C57BL/6 mice exposed to silica demonstrated upregulation of p16, p21, and tyrosine kinase Fgr by day 7, whereas thoracic irradiation induced p21 and Fgr by day 50 and p16 by day 110. Silica exposed GFP+ bone marrow chimeric C57BL/6 mice demonstrated senescent cells and gfp+/Fgr+ monocyte/macrophages in the lungs on day 21. The Fgr inhibitor TL02-59 abrogated monocyte/macrophages recruitment in in vitro transwell experiments.
CONCLUSION
Both silica and radiation exposure induce senescence and upregulate tyrosine kinase Fgr for the recruitment of bone marrow-derived monocyte/macrophages and the development of pulmonary fibrosis.
背景/目的：衰老和骨髓来源细胞在二氧化硅诱导的肺纤维化中的作用尚不清楚。
材料和方法
C57BL/6HNsd、p16 和 tdTOMp16+ 小鼠经气管内注射 200mg/kg 结晶二氧化硅或胸部放射（20Gy），并进行肺纤维化的发展研究。
结果
p16 小鼠在二氧化硅暴露后第 7 天表现出衰老。C57BL/6 小鼠在暴露于二氧化硅后第 7 天表现出 p16、p21 和酪氨酸激酶 Fgr 的上调，而胸部照射在第 50 天诱导 p21 和 Fgr，在第 110 天诱导 p16。在第 21 天，GFP+骨髓嵌合 C57BL/6 小鼠的二氧化硅暴露显示肺部有衰老细胞和 gfp+/Fgr+单核细胞/巨噬细胞。Fgr 抑制剂 TL02-59 可消除体外 Transwell 实验中单核细胞/巨噬细胞的募集。
结论
二氧化硅和辐射暴露均可诱导衰老，并上调酪氨酸激酶 Fgr，以募集骨髓来源的单核细胞/巨噬细胞并导致肺纤维化的发生。
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