PT - JOURNAL ARTICLE AU - AMITAVA MUKHERJEE AU - MICHAEL W. EPPERLY AU - RENEE FISHER AU - WEN HOU AU - DONNA SHIELDS AU - HONG WANG AU - JOEL S. GREENBERGER AU - LUIS A. ORTIZ TI - Silica Induced Lung Fibrosis Is Associated With Senescence, Fgr, and Recruitment of Bone Marrow Monocyte/Macrophages AID - 10.21873/invivo.12601 DP - 2021 Nov 01 TA - In Vivo PG - 3053--3066 VI - 35 IP - 6 4099 - http://iv.iiarjournals.org/content/35/6/3053.short 4100 - http://iv.iiarjournals.org/content/35/6/3053.full SO - In Vivo2021 Nov 01; 35 AB - Background/Aim: The role of senescence and bone marrow-derived cells in silica-induced pulmonary fibrosis is unknown. Materials and Methods: C57BL/6HNsd, p16+/LUC, 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+/LUC 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.