In TECs, HG stimulation increased pro-inflammatory/Th1/Th2 gene expression. Phosphorylation of signaling proteins shifted towards pro-inflammatory phenotype with suppressed phosphorylation of Th2 related signaling in TECs. Conclusion: These results suggest that pro-inflammatory axis induced by HG may play a role in the Ku-0059436 datasheet progression of diabetic nephropathy. JIN HUA, PIAO SHANG GUO, JIN JI ZHE, ZHENG HAI LAN, LI CAN YanBian University Hospital Introduction: Leflunomide
(LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. Methods: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of LEF and benazepril. Basic parameters Caspase inhibitor (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory (monocyte chemoattractant protein-1 [MCP-1] and Toll-like
receptor-2 [TLR-2]) and glomerulosclerotic factors (Transforming growth factor-beta1 [TGF-β1] and connective tissue growth factor [CTGF]), and oxidative stress (8-hydroxy-2¢-deoxyguanosine, 8-OHdG) were studied. Results: Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all P < 0.01).
Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β1 and CTGF) factors in diabetic rat kidney was reduced by treatment with either Ureohydrolase LEF or benazepril and was further reduced by the combined administration of the two drugs (P < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. Conclusion: LEF treatment lessens DN, and combined treatment with LEF and benazepril provided synergistic effects in preventing DN. HAGIWARA SHINJI1,2, MCCLELLAND AARON1, COOPER MARK1, TOMINO YASUHIKO2, PHILLIP KANTHARIDIS PHILLIP1 1JDRF Danielle Alberti Memorial Centre for Diabetes Complications, Diabetes Division, Baker IDI Heart and Diabetes Institute; 2Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine Introduction: MicroRNAs (miRNAs) are a novel class of non-coding RNA that regulate gene expression post-transcriptionally by cleavage or translational repression of specific target mRNAs.