Shared and Distinct Renal Transcriptome Signatures in 3 Standard Mouse Models of Chronic Kidney Disease.

Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to assess shared and distinct molecular changes in three mouse models commonly employed in preclinical CKD research and drug discovery.

Methods: All experiments were conducted on male C57BL/6J mice.

Semaglutide treatment attenuates vessel remodelling in ApoE-/- mice following vascular injury and blood flow perturbation.

Background And Aims: Randomized clinical studies have shown a reduction in cardiovascular outcomes with glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with the hypothesized mechanisms being an underlying effect on atherosclerosis. Here, we aimed to assess the pharmacological effects of semaglutide in an atheroprone murine model that recapitulates central mechanisms related to vascular smooth muscle cell (VSMC) phenotypic switching and endothelial dysfunction known to operate within the atherosclerotic plaque.

Methods: In study A, we employed an electrical current to the carotid artery in ApoE-/- mice to induce severe VSMC injury and death, after which the arteries were allowed to heal for 4 weeks.

Activation of the renal GLP-1R leads to expression of in the renal vascular tree.

The GLP-1 receptor (GLP-1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP-1R are elusive but may involve regulation of the renin-angiotensin-aldosterone system (RAAS). The expression of in the mouse renal vasculature was investigated by in situ hybridization after a single subcutaneous dose of liraglutide, semaglutide and after repeated injections of liraglutide.

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

The glucagon-like peptide-1 receptor (GLP1R) is expressed in the renal vasculature and known to be downregulated 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 GLP1R 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.

Liraglutide Improves the Kidney Function in a Murine Model of Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) is a global health burden, and the current treatment options only slow down the disease progression. GLP-1 receptor agonists (GLP-1 RA) have shown a renal protective effect in models of CKD; however, the mechanism behind the beneficial effect is not understood. In this study, we investigate the effect of the GLP-1 RA liraglutide in the nephrotoxic serum nephritis (NTN) CKD model.