Linagliptin ameliorates pulmonary fibrosis in systemic sclerosis mouse model via inhibition of endothelial-to-mesenchymal transition

被引:9
作者
Pei, Biwei [1 ]
Zhang, Na [1 ]
Pang, Tingting [1 ]
Sun, Gengyun [1 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Hefei 230022, Peoples R China
基金
中国国家自然科学基金;
关键词
Linagliptin; Pulmonary fibrosis; Systemic sclerosis; Endothelial-to-mesenchymal transition; Oxidative stress; INTERLEUKIN-6; PATHOGENESIS; PATHWAY; DPP-4;
D O I
10.1007/s11010-021-04349-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Systemic sclerosis (SSc) is a connective tissue disease that often causes pulmonary fibrosis. Dipeptidyl peptidase 4 (DPP4) inhibitor has shown anti-fibrotic properties in various fibrotic diseases. However, only two studies have reported its anti-fibrosis effects in pulmonary fibrosis, and the mechanism is not completely clear. In the present study, we further investigated the protective effects of linagliptin, a highly specific DPP4 inhibitor, on pulmonary fibrosis in SSc mouse model and the potential mechanisms. The results showed that linagliptin ameliorated pulmonary fibrosis in SSc mouse model, as evidenced by improved pathological changes of lung and body weight loss induced by BLM. Linagliptin also reduced BLM-induced oxidative stress, inflammation in lung in vivo. We revealed that linagliptin attenuated BLM-induced endothelial-to-mesenchymal transition (EndMT) in vitro and in vivo. BLM-induced enhanced migration ability of endothelial cells was also alleviated by linagliptin. Moreover, we confirmed that the Akt/mammalian target of rapamycin pathway was involved in BLM-induced EndMT in vivo, which was suppressed by linagliptin. In summary, we further confirmed the therapeutic effects of linagliptin on pulmonary fibrosis in SSc mouse model, which is based on its inhibitory effects on EndMT, oxidative stress, and inflammation.
引用
收藏
页码:995 / 1007
页数:13
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