Macrophage accumulation and renal fibrosis are independent of macrophage migration inhibitory factor in mouse obstructive nephropathy
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Updated: Aug 21, 2026
Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
Edwina K Rice1, David J Nikolic-Paterson, John R David
1Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Background And Aim:
The progression of renal injury, initiated by either an immune or non-immune insult, is closely associated with the accumulation of leucocytes and fibroblasts in the damaged kidney. Macrophage migration inhibitory factor (MIF) regulates leucocyte activation and fibroblast proliferation in vitro. Studies have identified a pathological role for MIF in immune-initiated renal injury in the rat. In this study, we examined the role of MIF in obstructive nephropathy, where renal injury is initiated by a non-immune insult.
Methods And Results:
Unilateral ureteric ligation was performed on MIF wildtype (+/+) and MIF deficient (-/-) mice. Groups of five mice were killed at days 0, 1, 5 or 10 after obstruction, and kidneys were examined via immunohistochemistry and northern blotting. In MIF +/+ mice, expression of the MIF protein increased in obstructed kidneys compared to normal control kidneys. Interstitial macrophage and T cell accumulation was significantly increased in obstructed kidneys at day 5 and 10, but was unaffected by MIF deficiency. Osteopontin and macrophage colony stimulating factor (M-CSF) mRNA expression in obstructed kidneys were equally increased in both genotypes, indicating that expression of these chemokines is not influenced by MIF. No difference was detected in the development of renal fibrosis in obstructed MIF +/+ and MIF -/- kidneys, as assessed by myofibroblast accumulation and proliferation and expression of profibrotic molecules (transforming growth factor-beta 1(TGF-beta1) and collagen).
Conclusion:
These results demonstrate that MIF expression is increased in obstructive nephropathy without affecting kidney leucocyte accumulation or the development of renal fibrosis. This suggests that the progression of renal injury in obstructive nephropathy is independent of MIF.
Insights
Macrophage migration inhibitory factor (MIF) increases in obstructive nephropathy but does not impact kidney injury progression. Renal fibrosis and leucocyte accumulation in obstructive nephropathy are independent of MIF.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Renal injury progression involves leucocyte and fibroblast accumulation.
- Macrophage migration inhibitory factor (MIF) regulates leucocyte activation and fibroblast proliferation.
- MIF plays a pathological role in immune-initiated renal injury.
Purpose of the Study:
- To investigate the role of MIF in obstructive nephropathy, a non-immune initiated renal injury model.
- To determine if MIF influences leucocyte accumulation and renal fibrosis in obstructive nephropathy.
Main Methods:
- Unilateral ureteric ligation was performed on MIF wildtype and deficient mice.
- Kidney tissues were analyzed using immunohistochemistry and northern blotting at various time points.
- Leucocyte infiltration, myofibroblast proliferation, and profibrotic gene expression were assessed.
Main Results:
- MIF protein expression increased in obstructed kidneys of wildtype mice.
- Leucocyte accumulation and renal fibrosis development were similar in both wildtype and MIF-deficient mice.
- Chemokine mRNA expression (Osteopontin, M-CSF) was not influenced by MIF deficiency.
Conclusions:
- MIF expression is upregulated in obstructive nephropathy.
- MIF deficiency does not alter leucocyte accumulation or renal fibrosis in this model.
- Renal injury progression in obstructive nephropathy is independent of MIF.
