Fig. 3: Renal tubule-specific Gcgr knockout ameliorated renal injury in DKD mice.
From: Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression
a Schematic of CRISPR/Cas9 constructs targeting Gcgr locus before/after Cre recombination. b Gcgr mRNA levels in primary PTECs and kidneys of 6-wk-old male Gcgrfl/fl and Gcgrfl/flKspCre mice on Normal Chow. c–e Renal Gcgr, p-Creb, total Creb protein via western blot. f–h UACR, urine Kim-1/creatinine, NAG/creatinine in different groups of mice. i 24 h urine volume in the indicated groups. j–k Kidney weight/body weight ratio and macro renal morphology in the indicated groups. l Kidney H&E, Oil Red O, PAS staining in the Gcgrfl/fl and Gcgrfl/flKspCre groups. Scale bar: 100 μm. m–n Renal Collagen I protein levels in kidneys from different groups of mice. o Masson and Sirius red staining of renal lesions in the Gcgrfl/fl and Gcgrfl/flKspCre groups. Scale bar: 100 μm. p TEM analyses of kidney proximal tubules. Scale bar: yellow: 5 μm; red: 2 μm; orange: 500 nm. Yellow arrow: lipid droplet. Quantitative analysis of the number of mitochondria per cell (q) and length of mitochondria (r). s TEM analyses of kidney glomeruli. Scale bar: 1 μm. White arrows: GBM; red asterisk: podocyte fusion. t–u Quantitative analysis of the GBM width and foot process width in the indicated groups. Mice were male and sampled after 8 weeks of STZ injections (c–p). The error bars represent the SEMs; n = 3 in each group (c–e, m–n), 5-9 in each group (b, f–j, q) and 12-15 in each group (r, t and u).
