Shah Sonal Navin, He Cijiang John, Klotman Paul
Mount Sinai School of Medicine, New York, NY 10029, USA.
Curr Opin Nephrol Hypertens. 2006 Jul;15(4):450-5. doi: 10.1097/01.mnh.0000232887.58271.67.
HIV-associated nephropathy is characterized by a constellation of pathologic findings including a collapsing glomerulopathy, tubular dilatation, and interstitial infiltration with leukocytes. This review summarizes some of the recent advances in our understanding of the gene products and signaling pathways that contribute to the pathogenesis of HIV-associated nephropathy.
Podocytes infected with HIV-associated nephropathy exhibit podocyte proliferation and de-differentiation. Restriction of HIV-1 transgene expression to the podocyte in a murine model supports the belief that podocyte infection is pivotal to the development of the disease. Recent studies have provided compelling in-vitro and in-vivo evidence that expression of the HIV-1 accessory gene nef is critical in altering the phenotype of mature podocytes and causing injury to these cells. An in-vitro study suggests that nef's effects in the podocyte appear to be mediated through Src kinase-dependent activation of the signal transducer and activator of transcription 3 and mitogen-activated protein kinase 1,2 signaling pathways.
Recent evidence demonstrates that the viral protein nef plays a critical role in the development of HIV-associated nephropathy and provides a foundation for developing new therapeutic strategies for patients afflicted with this disease.
HIV相关性肾病的特征是一系列病理表现，包括塌陷性肾小球病、肾小管扩张以及白细胞间质浸润。本综述总结了我们在理解导致HIV相关性肾病发病机制的基因产物和信号通路方面的一些最新进展。
感染HIV相关性肾病的足细胞表现出足细胞增殖和去分化。在小鼠模型中将HIV-1转基因表达限制在足细胞，支持了足细胞感染对疾病发展至关重要的观点。最近的研究提供了令人信服的体外和体内证据，表明HIV-1辅助基因nef的表达对于改变成熟足细胞的表型和对这些细胞造成损伤至关重要。一项体外研究表明，nef在足细胞中的作用似乎是通过Src激酶依赖性激活信号转导和转录激活因子3以及丝裂原活化蛋白激酶1、2信号通路介导的。
最近的证据表明，病毒蛋白nef在HIV相关性肾病的发展中起关键作用，并为为患有这种疾病的患者开发新的治疗策略提供了基础。
