Background

Idiopathic 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).

Methods

Idiopathic 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.

Results

Vildagliptin 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.

Conclusion

As an inhibitor of CD26/DPP4, Vildagliptin could be a promising therapeutic candidate for idiopathic pulmonary fibrosis.

中文翻译：

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CD26 / DPP4抑制剂维格列汀可通过调节细胞外基质改善博来霉素诱导的肺纤维化。

背景

特发性肺纤维化是一种使人衰弱的肺部疾病。CD26 / DPP4在肺损伤和纤维化中起促进作用。这项研究旨在探讨维格列汀在博来霉素诱导的肺纤维化中的作用，并探讨其对细胞外基质（ECM）的改善作用。

方法

通过气管内注射博来霉素诱导特发性肺纤维化小鼠模型。评估DPP4活性，并通过苏木精-曙红，Masson三色染色和羟脯氨酸分析研究纤维化。通过免疫化学和蛋白质印迹分析细胞外基质蛋白的表达，包括α-SMA，胶原蛋白IV，胶原蛋白I，FN和TGF-β。分类单核细胞，白细胞，嗜碱性粒细胞和淋巴细胞的百分比，并通过酶联免疫吸附法和蛋白质印迹法检测血浆和肺组织中的炎症因子。检测了维格列汀对TGF-β1诱导的MRC-5细胞增殖，分化和炎性因子的影响。

结果

维格列汀通过抑制CD26 / DPP4的活性，有效减轻了博来霉素诱导的肺组织的炎症和纤维化。维格列汀可抑制细胞外基质蛋白。因此，维达列汀有效地减轻了肺组织纤维化。

结论

作为CD26 / DPP4的抑制剂，维格列汀可能是特发性肺纤维化的有希望的治疗候选药物。