Macrophage accumulation and renal fibrosis are independent of macrophage migration inhibitory factor in mouse obstructive nephropathy.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Rice
Edwina K
EK
Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Nikolic-Paterson
David J
DJ
David
John R
JR
Bucala
Richard
R
Metz
Christine N
CN
Atkins
Robert C
RC
Tesch
Gregory H
GH
D000818:Animals; D005355:Fibrosis; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000502:physiology*; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014517:Ureteral Obstruction / Q000150:complications
D008263:Macrophage Migration-Inhibitory Factors