Related Experiment Video
Updated: Oct 5, 2026
Cannula Implantation into the Cisterna Magna of Rodents
Published on: May 23, 2018
Tubules are the major site of M-CSF production in experimental kidney disease: correlation with local macrophage
1Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Background:
Local proliferation of macrophages occurs within both the glomerulus and the interstitium in severe forms of human and experimental glomerulonephritis and plays an important role in amplifying renal injury. Macrophage colony-stimulating factor (M-CSF) is thought to be the growth factor driving this local macrophage proliferation. Previous studies have found that glomeruli are the predominant source of M-CSF production. However, this is difficult to reconcile with the prominent macrophage accumulation and proliferation seen in the interstitial compartment in glomerulonephritis. To address this issue, we localized M-CSF expression in rat models of glomerular versus tubulointerstitial injury and examined its relationship to local macrophage proliferation.
Methods:
M-CSF expression (Northern blotting, in situ hybridization, immunostaining, Western blotting) and local macrophage proliferation (double immunostaining) was examined in normal rat kidney on days 1 and 14 of rat anti-glomerular basement membrane (anti-GBM) glomerulonephritis and on day 5 following unilateral ureteric obstruction.
Results:
M-CSF mRNA and protein expression were identified in small numbers of glomerular podocytes, approximately 25% of cortical tubules, and most medullary tubules in normal rat kidney. Northern blotting showed a significant increase in whole kidney M-CSF mRNA in rat anti-GBM glomerulonephritis. Up-regulation of glomerular and, most prominently, tubular M-CSF production was confirmed by three independent methods: in situ hybridization, immunostaining, and Western blotting. The increase in M-CSF expression colocalized with local macrophage proliferation (ED1+PCNA+ cells) in both the glomerulus and tubulointerstitium. On day 5 after ureter ligation, there was a significant increase in tubular M-CSF mRNA and protein expression in the obstructed kidney, with no change in glomerular M-CSF. In parallel with M-CSF expression, macrophage accumulation and proliferation was prominent in the interstitium, but was absent from glomeruli.
Conclusions:
The tubular epithelial cell is the major site of M-CSF production within the injured kidney. Indeed, substantial macrophage accumulation and local proliferation can occur in the tubulointerstitium in the absence of glomerular inflammation. These results suggest that M-CSF production within the kidney, particularly by tubular epithelial cells, plays an important role in regulating local macrophage proliferation in experimental kidney disease.
Insights
In kidney disease, tubular cells, not glomeruli, are the main source of macrophage colony-stimulating factor (M-CSF). This M-CSF drives local macrophage proliferation in the tubulointerstitium, contributing to renal injury.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Macrophage proliferation in glomeruli and interstitium amplifies renal injury in glomerulonephritis.
- Macrophage colony-stimulating factor (M-CSF) is implicated in driving local macrophage proliferation.
- Previous findings of predominant glomerular M-CSF production conflicted with interstitial macrophage accumulation.
Purpose of the Study:
- To investigate M-CSF expression localization in rat kidneys with glomerular vs. tubulointerstitial injury.
- To examine the relationship between M-CSF expression and local macrophage proliferation.
Main Methods:
- Assessed M-CSF expression (mRNA and protein) using Northern blotting, in situ hybridization, immunostaining, and Western blotting.
- Evaluated local macrophage proliferation via double immunostaining for ED1 and PCNA.
- Utilized rat anti-glomerular basement membrane (anti-GBM) glomerulonephritis and unilateral ureteric obstruction models.
Main Results:
- M-CSF mRNA and protein were found in glomerular podocytes, cortical tubules, and medullary tubules in normal kidneys.
- Rat anti-GBM glomerulonephritis showed increased M-CSF mRNA in the whole kidney.
- Upregulated M-CSF production in glomeruli and tubules correlated with macrophage proliferation; prominent tubular M-CSF increase occurred after ureteric obstruction, with interstitial macrophage proliferation but no glomerular changes.
Conclusions:
- Tubular epithelial cells are the primary source of M-CSF in injured kidneys.
- Significant tubulointerstitial macrophage accumulation and proliferation can occur independently of glomerular inflammation.
- Kidney M-CSF production, especially by tubular cells, is crucial for regulating local macrophage proliferation in experimental kidney disease.
