Pirfenidone and nintedanib inhibit the lung alveolar regeneration in chronic pulmonary fibrosis mouse
10.16438/j.0513-4870.2020-0444
- VernacularTitle:吡非尼酮和尼达尼布抑制慢性肺纤维化小鼠肺泡上皮细胞再生
- Author:
Yun-xuan LI
1
;
Xiao-xi LÜ
1
;
Chang LIU
1
;
Shan-shan LIU
1
;
Zhuo-wei HU
1
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
alveolar epithelial type 2 cell;
pirfenidone;
nintedanib;
pulmonary fibrosis;
regeneration
- From:
Acta Pharmaceutica Sinica
2020;55(5):861-867
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.
