Decreased expression of the GLP-1 receptor after segmental artery injury in mice.

in Journal of Endocrinology
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  • 1 K Bjørnholm, Department of Experimental Animal Models , University of Copenhagen, Frederiksberg, 1870, Denmark
  • 2 G Povlsen, Department of Diabetes Pharmacology 1, Novo Nordisk, Måløv, Denmark
  • 3 M Ougaard, Department of Pathology and Imaging, Novo Nordisk, Måløv, Denmark
  • 4 C Pyke, Pathology and Imaging, Novo Nordisk, Måløv, Denmark
  • 5 G Rakipovski, Department of Cardiovascular Disease research, Novo Nordisk, Måløv, Denmark
  • 6 P Tveden-Nyborg, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
  • 7 J Lykksefeldt, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
  • 8 G Skovsted, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark

Correspondence: Katrine Bjørnholm, Email: katrine@dahlbjornholm.dk
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The glucagon-like peptide-1 receptor (GLP-1R) is expressed in the renal vasculature and known to be decreased under hypertensive conditions in rats and humans. However, little is known about the regulation in other types of renal pathology involving vascular changes. This study investigates the expression of the GLP-1R in renal vasculature after glomerular injury in the nephrotoxic nephritis mouse model, high cholesterol, and atherosclerosis in the Ldlr-/- mouse on western diet, and ex vivo injury in an organ culture model. The immunohistochemical signal of the GLP-1R was significantly decreased in arteries from mice with nephrotoxic nephritis after 42 days compared to 7 days and saline control (p<0.05). Histological evaluation of kidneys from Ldlr-/- mice on western diet showed a decreased GLP-1R specific immunohistochemical signal (p<0.05). The dilatory response to liraglutide was decreased in western diet fed Ldlr-/- mice compared to C57Bl/6J controls (p<0.05). Organ culture significantly decreased the immunohistochemical signal of the GLP-1R (p<0.05) and the expression of Glp-1r mRNA (p<0.005) compared to fresh. Organ cultured vessels showed vascular smooth muscle cell remodelling as Acta2 expression was decreased (p<0.005) and Ednrb was increased (p<0.05).

In conclusion, nephrotoxic nephritis and hypercholesterolemia led to decreased GLP-1R specific immunohistochemical signal. Ex vivo vascular injury in the organ culture model lead to a decrease in expression of GLP-R expression and contractile VSMC specific markers and increase in expression of dedifferentiation markers suggestive of an inverse relationship between phenotypic swich of the VSMC and the expression of the GLP-1R however, the causal relationship remains elusive.

 

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