| Background: Chronic allograft nephropathy (CAN) is the main disease causing graftloss nowadays. The mechanism of CAN is unclear. Osteopontin (OPN), apro-inflammatory and pro-fibrosis molecule, plays key role in late stage renal diseases.A potential role of OPN in the pathogenesis of CAN is investigated.Methods: F344 to Lewis rat CAN models were established. Left kidney was harvestedunder the surgical microscope. The graft was then transplanted to the recipient. 10 daysafter the surgery, the right kidney was cut off. All rats received CsA for 10 days. Shorthairpin RNA (shRNA) targeting OPN or negative control plasmid was injected into ratCAN models in vivo, through the renal vein following electroporation. 12 weeks later,serum and urine creatinine, BUN and urine protein was collected and examined to checkrenal function. Interstitial fibrosis (IF) and tubular atrophy (TA) were determined by HEand Masson's trichrome staining. Banff 97 standard was carried out to semi-quantifyIF/TA. Epithelial to mesenchymal transition (EMT) of the tubular epithelial cells wasdetermined by immunohistochemistry (IHC) and western blot.Results: 100 operations were carried out with 85% success rate. 12 weeks later, bychecking IHC and western blot, OPN expression of graft kidney was knocked down inRNA interference (RNAi) group. The TA/IF was significantly severer in Allo and NCgroup. However, histology observation showed that IF and TA was mild with a stablerenal function in the RNAi treated group. The Banff classification of RNAi group wassignificantly reduced compared with Allo group (79.4±3.2 vs 116.9±3.1, p<0.05). EMTof TECs was significantly slighter after knocking down of OPN, compared to CANmodels.Conclusion: OPN was upregulated in rat CAN models. Knocking down of OPN in vivocan protect the allograft from IF/TA and inhibit EMT process of the TECs in rats withCAN. OPN may be involved in CAN by promoting EMT of TECs. OPN may be served as a new therapeutic target of CAN. |
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