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Open Access Research

Dramatic early event in chronic allograft nephropathy: increased but not decreased expression of MMP-9 gene

Dongfeng Gu1, Yanling Shi2, Yanan Ding3, Xinyu Liu1 and Hequn Zou1*

Author affiliations

1 Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China

2 Department of Nephrology, Wenzhou Medical College, Wenzhou, 325035, People’s Republic of China

3 Department of Cardiovascular Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, People’s Republic of China

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Citation and License

Diagnostic Pathology 2013, 8:13  doi:10.1186/1746-1596-8-13

Published: 28 January 2013

Abstract

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 webcite.

Keywords:
Chronic allograft nephropathy (CAN); Mononuclear cells; Matrix metalloproteinase 9 (MMP-9); Transforming growth factor-beta1 (TGF-beta1); Smooth muscle cells (SMCs)