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

Abstract

ObjectiveThe 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.MethodsKidneys 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.ResultsThe 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.ConclusionsMMP-9 may play an important role in the mechanism of pathological changes during the earlier period of CAN.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1582313332832700.

Renal dysfunction and intragraft proMMP9 activity in renal transplant recipients with interstitial fibrosis and tubular atrophy

“…In addition, the significant correlation obtained between kidney proMMP9 and the GFR, a basic hallmark of renal dysfunction, suggests the involvement of MMPs in IF/TA development. In accordance with our results, an increased MMP9 expression in kidney allografts has been described as an early event in chronic allograft nephropathy in rats , in tight correlation with kidney mononuclear infiltration and TGFβ1 expression in the tubulo‐interstitium .…”

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

“…We speculate that the increase in active MMP-9 evident one week after KT likely originates from neutrophils in response to leukocyte activation inherent to I/R processes. This is supported by experimental studies demonstrating that MMP-9 promotes mononuclear cell infiltration in a rat model of early allograft nephropathy [43].…”

Clinical Significance of Monitoring Serum Level of Matrix Metalloproteinase 9 in Patients With Acute Kidney Allograft Rejection

“…Therefore, the role of the serum MMP-9 level after day 20 in acute renal allograft rejection requires further exploration. In addition, it has been shown that MMP-9 expression in renal allografts is also upregulated during chronic allograft nephropathy [23,24], whereas the serum MMP-9 level at this stage remains unclear.…”

“…Therefore, increased MMP-9 levels may promote the tissue infiltration of inflammatory cells, which then secrete more MMP-9 into the local environment, resulting in an amplification loop. In addition, it has been shown that increased MMP-9 expression may also induce the activation and replication of smooth muscle cells [23]. Therefore, MMP-9 might play an important role in the pathologic mechanism of renal allograft rejection, and thus could be a new potential target for treatment.…”