Potential role of senescent macrophages in radiation-induced pulmonary fibrosis

被引：108

作者：

Su, Lulu ^{[1
,2
]}

Dong, Yinping ^{[3
]}

Wang, Yueying ^{[3
]}

Wang, Yuquan ^{[1
,2
]}

Guan, Bowen ^{[1
,2
]}

Lu, Yanhua ^{[1
,2
]}

Wu, Jing ^{[3
]}

Wang, Xiaochun ^{[4
]}

Li, Deguan ^{[3
]}

Meng, Aimin ^{[1
,2
]}

Fan, Feiyue ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing Key Lab Anim Models Emerging & Remerging, Beijing 100021, Peoples R China

[2] Peking Union Med Coll, Comparat Med Ctr, NHC Key Lab Human Dis Comparat Med, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Inst Radiat Med, Tianjin Key Lab Radiat Med & Mol Nucl Med, Tianjin 300192, Peoples R China

[4] Beijing Inst Occupat Dis Prevent & Treatment, Beijing Prevent & Treatment Hosp Occupat Dis Chem, Beijing 100093, Peoples R China

来源：

CELL DEATH & DISEASE | 2021年 / 12卷 / 06期

基金：

中国国家自然科学基金;

关键词：

CELLULAR SENESCENCE; IONIZING-RADIATION; INHIBITION; MECHANISMS;

D O I：

10.1038/s41419-021-03811-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated beta -galactosidase (SA-beta -Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there's a significant increase in the expression of pro-fibrogenic factors (TGF-beta 1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1 alpha, Il-6, and Tnf-alpha), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10Gy IR. In addition, the percentages of SA-beta -Gal(+) senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF.

引用

页数：12

共 42 条

[1] IPF lung fibroblasts have a senescent phenotype [J].