Dramatic early event in chronic allograft nephropathy: increased but not decreased expression of MMP-9 gene.
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.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1582313332832700.
Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People's Republic of China.
Dongfeng
D
Gu
Yanling
Y
Shi
Yanan
Y
Ding
Xinyu
X
Liu
Hequn
H
Zou
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002465:Cell Movement; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005355:Fibrosis; D006084:Graft Rejection / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
D015415:Biomarkers; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D003404:Creatinine; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat