Long-Term Gene Therapy with Thrombospondin 2 Inhibits TGF-β Activation, Inflammation and Angiogenesis in Chronic Allograft Nephropathy

摘要: We recently identified Thrombospondin-2 (TSP-2) as a regulator of matrix remodelling and inflammation in experimental kidney disease by using TSP-2 null mice successfully proved overexpression therapeutic concept short term glomerulonephritis model the rat. In this current study, we investigated if long-term is also capable to ameliorate progression chronic setting allograft nephropathy F344-Lewis Two weeks after renal transplantation, two rat thigh muscles were transfected once only with either overexpressing plasmid (n = 8) or luciferase-expressing control (n = 8). Rats monitored for function, histological changes gene expression graft up 30 transplantation. Unexpectedly, treated group 2 rats died before end experiment function tended be worsened compared luciferase-treated controls. addition, glomerular sclerosis tubular interstitial injury well cortical fibronectin deposition was significantly increased kidneys despite reduced TGF-β activation marked anti-inflammatory (macrophages, T-cells B-cells) effects group. Long-term therapy impaired repair endothelium, demonstrated significant higher peritubular endothelial rarefaction cell proliferation transplanted from This effect associated decreased levels VEGF but not VEGF1 receptor. conclusion, its blocking effects, did rather most likely via anti-angiogenic properties on microvasculature.