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SHR Neuro Krebs Kardio Lipid

Moschovaki Filippidou, F; Kirsch, AH; Thelen, M; Kétszeri, M; Artinger, K; Aringer, I; Schabhüttl, C; Mooslechner, AA; Frauscher, B; Pollheimer, M; Niedrist, T; Meinitzer, A; Drucker, DJ; Pieber, TR; Eller, P; Rosenkranz, AR; Heinemann, A; Eller, K.
Glucagon-Like Peptide-1 Receptor Agonism Improves Nephrotoxic Serum Nephritis by Inhibiting T-Cell Proliferation.
Am J Pathol. 2020; 190(2):400-411 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Aringer Ida
Artinger Katharina
Eller Kathrin
Eller Philipp
Frauscher Bianca
Heinemann Akos
Ketszeri Mate Csaba
Kirsch Alexander
Meinitzer Andreas
Mooslechner Agnes Anna
Moschovaki Filippidou Foteini
Niedrist Tobias
Pieber Thomas
Pollheimer Marion
Rosenkranz Alexander
Schabhüttl Corinna
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Abstract:
Glucagon-like peptide (GLP)-1 analogs such as liraglutide improved albuminuria in patients with type 2 diabetes in large randomized controlled trials. One of the suspected mechanisms is the anti-inflammatory potential of GLP-1 receptor (Glp1r) agonism. Thus, the anti-inflammatory action of Glp1r agonism was tested in a nondiabetic, T-cell-mediated murine model of nephrotoxic serum nephritis (NTS). The role of Glp1r in NTS was evaluated by using Glp1r-/- mice or C57BL/6 mice treated with liraglutide. In vitro, murine T cells were stimulated in the presence of liraglutide or vehicle. Glp1r-/- mice displayed increased renal infiltration of neutrophils and T cells after induction of NTS. Splenocyte proliferation and TH1 cytokine transcription were increased in spleen and lymph nodes of Glp1r-/- mice. Liraglutide treatment significantly improved the renal outcome of NTS in C57BL/6 mice by decreasing renal infiltration and proliferation of T cells, which resulted in decreased macrophage infiltration. In vitro, T cells stimulated in the presence of liraglutide showed decreased proliferation of TH1 and TH17 cells. Liraglutide blocked glycolysis in T cells and decreased their Glut1 mRNA expression. Together, Glp1r agonism protects mice from a T-cell-dependent glomerulonephritis model by inhibition of T-cell proliferation, possibly by interacting with their metabolic program. This mechanism may explain in part the renoprotective effects of Glp1r agonism in diabetic nephropathy. Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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