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Updated: May 14, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Dramatic early event in chronic allograft nephropathy: increased but not decreased expression of MMP-9 gene
Dongfeng Gu1, Yanling Shi, Yanan Ding
1Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People's Republic of China.
Objective:
The infiltration of mononuclear cells and replication and migration of smooth muscle cells (SMCs) from media into the intima in the vascular wall are the cardinal pathological changes in the early stage of chronic allograft nephropathy (CAN). But the mechanism is unclear. Therefore we investigated the role of matrix metalloproteinase 9 (MMP-9) and its interaction with TGF-beta1, tubulointerstitial mononuclear cells infiltration and migration of SMCs in the early stage of CAN.
Methods:
Kidneys of Fisher (F334) rats were orthotopically transplanted into bilaterally nephrectomized Lewis (LEW) recipients. To suppress an initial episode of acute rejection, rats were briefly treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days. Animals were harvested at 12 weeks after transplantation for histological, immunohistochemistry and molecular biological analysis.
Results:
The expression of MMP-9 was up-regulated in interstitium and vascular wall in the early stage of CAN, where there were interstitial mononuclear cells infiltration and SMCs migration and proliferation. Moreover the expression of MMP-9 were positively correlated with the degree of interstitial mononuclear cells infiltration, the quantity of SMCs in arteriolar wall, and also the increased TFG-beta1 expression in the tubulointerstitium and arteriolar wall.
Conclusions:
MMP-9 may play an important role in the mechanism of pathological changes during the earlier period of CAN.
Virtual Slides:
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1582313332832700.
Insights
Matrix metalloproteinase 9 (MMP-9) is upregulated in chronic allograft nephropathy (CAN), correlating with mononuclear cell infiltration and smooth muscle cell migration. MMP-9 plays a key role in early CAN pathological changes.
Area of Science:
- Nephrology
- Immunology
- Vascular Biology
Background:
- Chronic allograft nephropathy (CAN) involves mononuclear cell infiltration and smooth muscle cell (SMC) migration into the vascular intima.
- The underlying mechanisms of these early pathological changes in CAN remain unclear.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase 9 (MMP-9) in the early stages of CAN.
- To explore the interaction between MMP-9, TGF-beta1, tubulointerstitial mononuclear cells, and SMC migration in CAN.
Main Methods:
- Orthotopic kidney transplantation model in Fisher (F334) rats into Lewis (LEW) recipients.
- Short-term cyclosporine A treatment to prevent acute rejection.
- Analysis at 12 weeks post-transplantation using histology, immunohistochemistry, and molecular biology.
Main Results:
- MMP-9 expression was elevated in the interstitium and vascular wall during early CAN.
- Upregulated MMP-9 correlated positively with interstitial mononuclear cell infiltration and SMC quantity in arterioles.
- MMP-9 expression also correlated with increased TGF-beta1 levels in the tubulointerstitium and arteriolar wall.
Conclusions:
- Matrix metalloproteinase 9 (MMP-9) appears to be significantly involved in the pathological mechanisms of early chronic allograft nephropathy.
- MMP-9 may contribute to mononuclear cell infiltration and smooth muscle cell migration in CAN.
