linagliptin and Pulmonary-Fibrosis

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.

Topics: Animals; Bleomycin; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Endothelial Cells; Female; Linagliptin; Mice; Pulmonary Fibrosis; Scleroderma, Systemic

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ This article has been retracted due to the authors’ plagiarism of text and images from the work of Eman Said Abd-Elkhalek, Hatem Abdel-Rahman Salem, Ghada Mohamed SuddeK, Marwa Ahmed Zaghloul and Ramy Ahmed Abdel-Salam, Faculties of Pharmacy and Medicine, Mansoura University, Mansoura, Egypt.

Topics: Animals; Bleomycin; Body Weight; Calcitriol; Drug Therapy, Combination; In Vitro Techniques; Linagliptin; Male; Mice; Organ Size; Pulmonary Fibrosis