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Int. Immunopharmacol. · Oct 2020
Vildagliptin, a CD26/DPP4 inhibitor, ameliorates bleomycin-induced pulmonary fibrosis via regulating the extracellular matrix.
- Yang Liu and Yongchao Qi.
- Medical College of Pingdingshan University, Chongwen Road, Xinhua District, Pingdingshan City, Henan 467000, China.
- Int. Immunopharmacol. 2020 Oct 1; 87: 106774.
BackgroundIdiopathic pulmonary fibrosis is a debilitating lung disease. CD26/DPP4 plays promotive roles in pulmonary damage and fibrosis. This study aimed to explore the roles of vildagliptin in bleomycin-induced pulmonary fibrosis, and to address its ameliorative effect on the extracellular matrix (ECM).MethodsIdiopathic pulmonary fibrosis mice models were induced by intratracheal injection of bleomycin. DPP4 activity was evaluated, and the fibrosis was investigated by Hematoxylin-eosin, Masson's trichrome staining and hydroxyproline assay. Expression of extracellular matrix proteins including α-SMA, collagen IV, collagen I, FN and TGF-β were analyzed by immunochemistry and western blot. Percentages of the numbers of monocytes, leukocytes, basophils and lymphocytes were classified, and inflammatory factors in plasma as well as lung tissues were examined by enzyme-linked immunosorbent assay and western blot. The influences of vildagliptin on TGF-β1-induced cell proliferation, differentiation and inflammatory factors in MRC-5 cells were detected.ResultsVildagliptin effectively attenuated inflammation and fibrosis in bleomycin-induced pulmonary tissue via inhibiting the activity of CD26/DPP4. extracellular matrix proteins were suppressed by vildagliptin. Thus, lung tissue fibrosis was efficiently alleviated by vildagliptin.ConclusionAs an inhibitor of CD26/DPP4, Vildagliptin could be a promising therapeutic candidate for idiopathic pulmonary fibrosis.Copyright © 2020 Elsevier B.V. All rights reserved.
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