Lu Ting-Chi, He John Cijiang, Klotman Paul E
Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Nephron Clin Pract. 2007;106(2):c67-71. doi: 10.1159/000101800. Epub 2007 Jun 6.
HIV-associated nephropathy (HIVAN) is the leading cause of end-stage renal failure in HIV-1 seropositive patients. The pathologic findings include collapsing focal segmental glomerulosclerosis with proliferation of epithelial cells in Bowman's space. Anatomically, these cells correspond to podocytes and exhibit a unique phenotype with loss of many differentiation markers including synaptopodin and dysregulation of the cell cycle markers consistent with proliferation. Podocyte dysfunction appears to be a direct result of HIV-1 protein expression, specifically Nef and Vpr as well as specific host factors that have yet to be elucidated. The mechanism by which Nef induces podocyte proliferation and dedifferentiation has been traced to its ability to activate several signaling pathways including Src-Stat3 and ras-raf-MAPK1, 2. Activation of the cAMP/PKA pathway with all-trans-retinoic acid appears to modulate these changes and returns podocytes to a differentiated, nonproliferating phenotype.
人类免疫缺陷病毒相关性肾病（HIVAN）是HIV-1血清阳性患者终末期肾衰竭的主要原因。病理表现包括塌陷型局灶节段性肾小球硬化，伴鲍曼间隙上皮细胞增殖。从解剖学上看，这些细胞对应于足细胞，表现出独特的表型，许多分化标志物缺失，包括突触素，且细胞周期标志物失调，与增殖一致。足细胞功能障碍似乎是HIV-1蛋白表达的直接结果，特别是Nef和Vpr以及尚未阐明的特定宿主因子。Nef诱导足细胞增殖和去分化的机制已追溯到其激活多种信号通路的能力，包括Src-Stat3和ras-raf-MAPK1、2。用全反式维甲酸激活cAMP/PKA通路似乎可调节这些变化，并使足细胞恢复到分化的、非增殖的表型。
