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Conservation of glucagon like peptide-1 level with liraglutide and linagilptin protects the kidney against angiotensin II-induced tissue fibrosis in rats.

Authors
  • Bai, Feng1
  • Zhang, Li-Hui1
  • Zhang, Wei-Wei1
  • Zheng, Rong-Hua1
  • Eskew, Joshua Robert1
  • Bennett, Josiah1
  • Wang, Ning-Ping1
  • Bose, Himangshu S1
  • Zhao, Zhi-Qing2
  • 1 Cardiovascular Research Laboratory, Mercer University School Medicine, Savannah, GA, USA.
  • 2 Cardiovascular Research Laboratory, Mercer University School Medicine, Savannah, GA, USA. Electronic address: [email protected]
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Dec 04, 2019
Volume
867
Pages
172844–172844
Identifiers
DOI: 10.1016/j.ejphar.2019.172844
PMID: 31811859
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

This study tested the hypothesis that the enhancement of glucagon-like peptide-1 (GLP-1) level through either exogenous supply of GLP-1 agonist, liraglutide or prevention of endogenous GLP-1 degradation with dipeptidyl peptidease-4 inhibitor, lingaliptin ameliorates angiotensin II (Ang II)-induced renal fibrosis. Sprague-Dawley rats were randomly divided into four groups: 0.9% saline or Ang II (500 ng/kg/min) was infused with osmotic minipumps for 4 weeks, defined as sham and Ang II groups. In drug treated groups, liraglutide (0.3 mg/kg) was injected subcutaneously twice daily or linagliptin (8 mg/kg) was administered daily via oral gavage during Ang II infusion. Compared with Ang II stimulation, liraglutide or linagliptin comparatively down-regulated the protein level of the AT1 receptor, and up-regulated the AT2 receptor, as identified by a reduced AT1/AT2 ratio (all p < 0.05), consistent with less locally-expressed AT1 receptor and enhanced AT2 receptor in the glomerular capillaries and proximal tubules of the renal cortex. Furthermore, both drugs significantly increased the expression of GLP-1 receptor and attenuated the protein levels of TLR4, NOX4 and IL-6. The populations of macrophages and α-SMA expressing myofibroblasts decreased with treatment of liraglutide and linagliptin, in coincidence with the reduced expression of phosphor-Smad2/3, Smad4, TGFβ1, and up-regulated Smad7. Along with these modulations, renal morphology was preserved and synthesis of fibronectin/collagen I was down-regulated, as identified by small collagen-rich area in the renal cortex. These results suggest that the preservation of GLP-1 level using liraglutide or linagliptin might be considered as an add-on therapeutic option for inhibiting Ang II induced renal fibrosis and failure. Copyright © 2019 Elsevier B.V. All rights reserved.

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