A recent publication from Anna-Lena Mayer et al. in the British Journal of Pharmacology demonstrated how dipeptidyl peptidase 4 (DPP-4) inhibitors improved the resolution of glomerular injury in a rat glomerular nephritis model induced by Chondrex, Inc.’s rat nephritogenic monoclonal antibody, a84.
High expression of DPP-4 is found in the crescents of glomeruli from patients with glomerulonephritis. DPP-4, which is an exopeptidase, cleaves a wide range of other substrates including peptide hormones such as stromal-derived factor 1 alpha (SDF-1α; CXCL12 α) or monocyte chemoattractant protein 1 (MCP-1 or CCL2). The roles of renal DPP-4 in the pathogenesis of glomerular diseases and the potential therapeutic effects of DPP-4 inhibition are still under investigation.
Rat glomerular nephritis was established in male Wistar Kyoto rats who received a single intravenous tail vein injection of a84 antibody specific for α4(IV)NC1 in the rat glomerular basement membrane. The short term (7-14 days) and long-term (3-8 weeks) experimental groups were established for evaluating the effects of the effects of DPP-4 inhibition. In the short-term group, the DPP-4 inhibition significantly reduced proteinuria and serum urea levels by Day 14 (therapeutic). On the other hand, in the long-term group, DPP-4 inhibition resulted in 25% lower proteinuria levels by the 3-5 weeks timepoint (preventative). Furthermore, DPP-4 function and glomeruli fibrosis was evaluated by serum chemokine levels and Sirius Red staining, respectively.
For more information, please refer to the following link.
A.-L. Mayer, I. Scheitacker, N. Ebert, T. Klein, K. Amann, C. Daniel, The dipeptidyl peptidase 4 inhibitor linagliptin ameliorates renal injury and accelerated resolution in a rat model of crescentic nephritis. Br. J. Pharmacol. 178, 878–895 (2021).
In order to study the therapeutic effects of new compounds against rat glomerulonephritis, Chondrex, Inc. provides several different types of nephritogenic monoclonal antibodies which induce varying levels of rat glomerulonephritis. Nephritis can be developed in a couple of days and can last longer than eight weeks. Chondrex, Inc. also provides other nephritis evaluation tools for tracking levels of urinary protein, cytokines/chemokines, and collagen deposition. Please refer to Chondrex, Inc’s website for more information.