Investigation of a novel therapy for renal diseases by inhibiting CTGF

结缔组织生长因子（CTGF/CCN 2）调节其他生长因子的信号传导并促进纤维化。我们研究了CTGF在糖尿病肾病和抗肾小球基底膜（抗GBM）肾炎中的作用，使用条件性CTGF敲除小鼠。全身诱导CTGF敲除（ROSA-CTGF cKO）小鼠和足细胞特异性CTGF敲除小鼠在链脲佐菌素诱导的糖尿病肾病中未表现出明显的表型变化。在抗GBM肾炎模型中，ROSA-CTGF cKO小鼠与对照小鼠相比，蛋白尿减少50%，肾小球中巨噬细胞浸润减少40%，肾小球改变包括新月体形成、细胞外基质沉积和电镜分析中GBM厚度。

Connective tissue growth factor (CTGF/CCN2) regulates signaling of other growth factors and promotes fibrosis. We examined the role of CTGF in diabetic nephropathy and in anti-glomerular basement membrane (anti-GBM) nephritis, using conditional CTGF knockout mice. Systemic inducible CTGF knockout (ROSA-CTGF cKO) mice and podocyte-specific CTGF knockout mice exhibited no apparent phenotypic changes in streptozotocin-induced diabetic nephropathy. In anti-GBM nephritis model, ROSA-CTGF cKO mice ameliorated proteinuria by 50%, macrophage infiltration in glomeruli by 40%, glomerular changes including crescentic formation, extracellular matrix deposition and thickness of GBM in electron microscopic analysis compared with control mice.