The cell cycle inhibitor p21 promote mouse lung fibrosis by activating alveolar macrophages
10.16438/j.0513-4870.2019-0965
- VernacularTitle:细胞周期抑制因子p21活化巨噬细胞促进小鼠肺纤维化发生发展
- Author:
Xu-peng WEI
1
;
Wan-yu WANG
2
;
Yun-xuan LI
2
;
Chang LIU
2
;
Xiao-xi LÜ
2
;
Yan-yan ZHAO
1
;
Shan-shan LIU
2
Author Information
1. Pharmacy College, Hebei University, Baoding 071000, China
2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
lung fibrosis;
macrophage;
p21;
fibroblast activation;
bleomycin injury
- From:
Acta Pharmaceutica Sinica
2020;55(8):1792-1800
- CountryChina
- Language:Chinese
-
Abstract:
This study was to determine the expression of the cell cycle inhibitor p21 in alveolar macrophages (AMs) and the role of p21 in activation of AMs in bleomycin (BLM) injury-induced lung fibrosis. The expression of CD206 in AMs was measured by immunofluorescence staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of macrophage activation markers. The coculture assay for macrophage and fibroblast was employed to explore the effect of macrophage on fibroblast activation. Immunofluorescence staining and western blotting assay were adopted to detect the expression of p21 in fibrotic tissues. AMs were treated with p21 knockdown or overexpression virus, RT-PCR and the co-culture system were used to explore the effect of p21 expression on macrophage activation. The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. Our results showed that the expression of CD206 and macrophage activation markers was increased in AMs from fibrotic mice, indicating that AMs from fibrotic mice were associated with a profibrotic phenotype. Moreover, the expression of p21 was upregulated in AMs after BLM treatment. Depletion of p21 suppressed macrophage activation, while overexpression of p21 promoted the profibrotic phenotype of AMs from healthy mice. In summary, BLM injury causes the progressive accumulation of p21 in AMs, which induces the production of a number of profibrotic factors promoting the development of pulmonary fibrosis.
