Figure 1. The e/e loss-of-function mutation of MC1R aggravates proteinuria, kidney injury and dysfunction in murine models of nephrotoxic serum (NTS) nephritis, and blunts the protective efficacy of melanocortin therapy.

(a) Schematic diagram depicts the animal study design. Wild-type (WT) and MC1R-null (e/e) mice received an intraperitoneal injection of 250μl rabbit IgG emulsified in complete Freund’s adjuvant (CFA) 6 days before a tail vein injection of either rabbit NTS or nonimmune IgG, followed by treatment with repository corticotropin injection (RCI), vehicle gel (Veh gel), the pan-melanocortin receptor agonist [Nle, DPhe]-α-MSH (NDP-MSH), MC1R agonist MS05 (custom-made peptide, GL Biochem), or vehicle (Veh) till day 14. (b) Proteinuria was estimated using the urinary albumin-to-creatinine ratios (uACR). (c) Kidney function was assessed by measuring blood urea nitrogen (BUN) levels in sera. (d) Representative micrographs of periodic acid-Schiff staining of mouse kidneys are shown. Arrowheads indicate glomeruli with crescents (Scale bar = 50 μm). (e~g) Semi-quantitative morphometric analysis of (e) glomerulonephritis (GN) score, (f) tubulointerstitial nephritis (TIN) score, and (g) the percentage of glomeruli with crescents based on periodic acid-Schiff staining of mouse kidneys. *P<0.05 by analysis of variance. ^aP<0.05 versus e/e group treated with NTS and Veh gel or WT group with NTS and RCI treatment; ^bP<0.05 versus e/e mice treated with NTS and RCI; ^cP<0.05 versus e/e mice treated with NTS and Veh or WT mice treated with NTS and NDP-MSH or MS05; ^dP<0.05 versus e/e mice treated with NTS and NDP-MSH; (n=6). q.o.d., every other day; s.c., subcutaneous. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.