Fig. 4.

Labeled CoRL decrease in the extraglomerular vascular smooth muscle compartment, and increase in the intraglomerular compartment in aging nephropathy. A–E: representative pictures of kidneys from mice aged 4, 12, 52, and 64 wk. A: low-magnification image (×100) from a 4-wk-old kidney shows that CoRL are permanently labeled with ZsGreen reporter in the extraglomerular vascular smooth muscle compartment. They were rarely detected in the intraglomerular compartment and are faintly detected in the tubular compartment. B: low magnification image (×100) from a 12 wk kidney shows a similar distribution of reporter labeled CoRL to 4 wk kidneys shown in A. C: at 52 wk, reporter labeled CoRL decrease in the extraglomerular vascular smooth muscle compartment. Labeled reporter cells were still rarely detected in glomeruli and in tubules. D: at 64 wk, reporter labeled CoRL remained decreased in the extraglomerular vascular smooth muscle compartment. However, there was a paradoxical increase in the number of reporter labeled CoRL in the intraglomerular compartment (labeled g). E: glomerulus from a 64-wk-old kidney viewed at higher magnification (×630) shows a number of reporter-labeled cells (green) in the intraglomerular compartment, which were in a characteristic podocyte distribution pattern. F: number of ZsGreen reporter-labeled CoRL was quantitated in Ren1cCre × Rs-ZsGreen-R reporter mice. Compared with 4 and 12 wk of age, the number of ZsGreen-labeled cells decreased significantly in the extraglomerular vascular smooth muscle compartment at 52 and 64 wk (shaded bars). In contrast, there was an increase in the number of reporter labeled CoRL in the glomerular tuft (black bars) at 64 wk. G–L: representative images of double staining for renin and ZsGreen reporter. G: lower magnification shows the distribution of CoRL reporter (green) was restricted to the extraglomerular vascular smooth muscle compartment (arrows indicate examples). H: distribution of renin staining (red) was also restricted to the extraglomerular vascular smooth muscle compartment (arrows indicate examples). I: merged image shows clear overlap of renin staining and the reporter (yellow, arrows indicate examples). Red blood cell autofluorescence appears orange in color. J–L: higher magnification images of the glomerulus indicated by the white boxes in G–I, respectively. These data show that renin staining is restricted to the extraglomerular compartment and that when labeled CoRL migrate to the glomerulus they do not stain for renin.