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BioMed Research International
Volume 2018, Article ID 1864107, 14 pages
https://doi.org/10.1155/2018/1864107
Research Article

Glucagon-Like Peptide-1 Mediates the Protective Effect of the Dipeptidyl Peptidase IV Inhibitor on Renal Fibrosis via Reducing the Phenotypic Conversion of Renal Microvascular Cells in Monocrotaline-Treated Rats

1Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
2Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Correspondence should be addressed to Hong Wang; nc.ude.umjn@gnawgnoh and Xiangrong Zuo; moc.liamg@ouzgnorgnaix

Received 21 June 2017; Revised 24 November 2017; Accepted 4 December 2017; Published 23 January 2018

Academic Editor: Bo Zuo

Copyright © 2018 Jian Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis. These effects of sitagliptin were mediated by glucagon-like peptide-1 receptor (GLP-1R), since they were blocked by the GLP-1R antagonist exendin-3 (Ex-3, 40 ug/kg/d). The GLP-1R agonist liraglutide showed a similar renal protective effect in a dose-independent manner. In addition, sitagliptin, as well as liraglutide, alleviated the MCT-induced apoptosis of renal cells by increasing the expression of survival factor glucose-regulated protein 78 (GRP78), which was abolished by the GLP-1R antagonist Ex-3. Sitagliptin and liraglutide also effectively ameliorated the conversion of vascular smooth muscle cells (SMCs) from a synthetic phenotype to contractile phenotype. Moreover, sitagliptin and liraglutide inhibited endothelial-mesenchymal transition (EndMT) via downregulating transforming growth factor-β1 (TGF-β1). Collectively, these findings suggest that DPP-4 inhibition can reduce microcirculation lesion-induced renal fibrosis in a GLP-1-dependent manner.