Histopathological and molecular analysis of idiopathic pulmonary fibrosis lungs from patients treated with pirfenidone or nintedanib

被引:20
作者
Zhang, Yingwei [1 ,2 ]
Jones, Kirk D. [3 ]
Achtar-Zadeh, Natalia [1 ]
Green, Gary [1 ]
Kukreja, Jasleen [4 ]
Xu, Biyun [2 ]
Wolters, Paul J. [1 ]
机构
[1] Univ Calif San Francisco, Dept Med, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA
[2] Nanjing Univ, Med Sch, Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China
[3] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA
[4] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA
关键词
antifibrotic; idiopathic pulmonary fibrosis; senescence; telomere; OBSERVATIONAL COHORT; TELOMERE LENGTH; PATHOGENESIS; INHIBITION; INJURY; RISK;
D O I
10.1111/his.13745
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims The objective of this study was to quantify the impact of pirfenidone or nintedanib treatment on lung histopathology and molecular mediators of fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Methods and results We collected lung tissue from IPF patients at the time of lung transplantation. Histopathological changes were quantified using a blinded scoring method. Proteins associated with senescence or active TGF-beta were quantified in lung tissues by immunoblot and immunostaining. Histopathological quantification showed similar amounts of dense collagen fibrosis, fibroblast foci and alveolar macrophages in untreated or pirfenidone- or nintedanib-treated IPF patients. There was less diffuse alveolar damage and organising pneumonia in pirfenidone-treated IPF patients. Lungs of nintedanib-treated patients had a trend towards less lymphocytic interstitial infiltration. There was no difference in expression of p-SMAD3, p21 or p16 in the lungs of untreated, pirfenidone- or nintedanib-treated IPF patients. Alveolar epithelial cells, but not fibroblast foci, were immunoreactive to p16. Pirfenidone or nintedanib treatment did not inhibit activation of senescence programming in cultured lung epithelial cells mediated by hydrogen peroxide. Conclusion Pirfenidone and nintedanib do not modulate expression of senescence markers, levels of p-SMAD3 or the amount of fibrosis in IPF lungs. Treated patients have less histopathological evidence of acute lung injury at the time of lung transplantation.
引用
收藏
页码:341 / 349
页数:9
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