Wagrowska-Danilewicz M, Danilewicz M
Department of Nephropathology, Medical University of Lodz, Lodz, Poland.
Nefrologia. 2007;27(6):710-5.
Synaptopodin is protein of podocytes, and a part of the actin-based contractile apparatus of foot-processes. Recently, proteins expressed by the podocyte were found to be important for the integrity of the glomerular filtration barrier. Podocytes are injured in many forms of glomerulopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The study was undertaken to determinate if synaptopodin immunoexpression in renal tissue specimens differs between patients with steroid-responsive MCD, steroid-resistant MCD, and FSGS.
Synaptopodin immunoexpression was evaluated by immunoperioxidase staining with a mouse anti-human monoclonal antibody in 12 renal biopsy specimens in patients with steroid-responsive MCD, 10 renal tissues in steroid-resistant MCD, and in 14 renal biopsy specimens in patients with FSGS. As a control 10 tissue specimens of the kidneys removed because of trauma were used. Synaptopodin expression was quantified as a percentage of glomerular tuft by computerized image analysis system.
In normal controls synaptopodin immunoexpression was seen in podocytes along the glomerular basement membrane in a finely linear pattern. No changes were found in synaptopodin immunoexpression in steroid-responsive MCD versus controls. In patients with steroid-resistant MCD and FSGS a granular pattern of synaptopodin immunoexpression was seen. Areas of sclerosis in patients with FSGS did not demonstrate synaptopodin expression. Statistical analysis showed significantly diminished synaptopodin immunoexpresion in glomeruli in patients with steroid-resistant MCD and FSGS as compared with steroid-responsive MCD group and controls. Moreover, in renal tissues in patients with FSGS the immunoexpression of synaptopodin was decreased in comparison with renal biopsies in patients with steroid-resistant MCD.
our results suggest that abnormal distribution and reduced expression of synaptopodin may be associated with poor response to steroid therapy in MCD and FSGS.
突触足蛋白是足细胞的一种蛋白质,是足突肌动蛋白收缩装置的一部分。最近发现,足细胞表达的蛋白质对肾小球滤过屏障的完整性很重要。在多种肾小球疾病中,包括微小病变肾病(MCD)和局灶节段性肾小球硬化症(FSGS),足细胞都会受到损伤。本研究旨在确定肾组织标本中突触足蛋白的免疫表达在激素反应性MCD、激素抵抗性MCD和FSGS患者之间是否存在差异。
用小鼠抗人单克隆抗体通过免疫过氧化物酶染色评估12例激素反应性MCD患者的肾活检标本、10例激素抵抗性MCD患者的肾组织以及14例FSGS患者的肾活检标本中的突触足蛋白免疫表达。作为对照,使用了10例因外伤切除的肾脏组织标本。通过计算机图像分析系统将突触足蛋白的表达量化为肾小球簇的百分比。
在正常对照中,突触足蛋白的免疫表达沿肾小球基底膜呈细线性模式见于足细胞。激素反应性MCD与对照相比,突触足蛋白免疫表达未见变化。在激素抵抗性MCD和FSGS患者中,可见突触足蛋白免疫表达呈颗粒状。FSGS患者的硬化区域未显示突触足蛋白表达。统计分析显示,与激素反应性MCD组和对照组相比,激素抵抗性MCD和FSGS患者肾小球中的突触足蛋白免疫表达明显减少。此外,与激素抵抗性MCD患者的肾活检相比,FSGS患者肾组织中突触足蛋白的免疫表达降低。
我们的结果表明,突触足蛋白的异常分布和表达降低可能与MCD和FSGS中激素治疗反应不佳有关。