【摘要】 目的:FSGS以足细胞损伤为突出特点,但肾小管上皮细胞损伤在这类患者很常见,而且蛋白尿的程度不足以解释其原因。由于足细胞和肾小管上皮细胞分享许多共同的分子,因此我们推测,这可能是导致FSGS状态下足细胞和肾小管上皮细胞同时损伤的分子基础。有关研究显示,IL-13可以通过作用于足细胞膜上的IL-13R,导致足细胞的损伤。本研究对FSGS患者肾小管上皮细胞IL-13R表达和分布情况进行观察,以期对上述问题加以探讨。方法:选择肾活检明确诊断的特发性FSGS(n=41)患者,并排除继发性因素。对照选取伴大量蛋白尿的IgA肾病(IgAN,n=11)和膜性肾病(MN,n=10)患者。正常对照选择肾移植供体(n=5)。FSGS患者小管间质病变分为:"正常"、急性病变、急性+慢性病变、慢性病变。IL-13R和RANTES染色采用间接免疫荧光法。IL-13R表达分布和强度采用评分方法。IL-13R与N-cadherin免疫荧光双标观察IL-13R在小管上皮细胞的分布。结果:正常对照组近端肾小管上皮细胞表达IL-13R,但分布局限,而且强度弱。疾病对照组仅少数肾小管上皮细胞可见中等量IL-13R表达,但强度较弱。FSGS患者近端肾小管上皮细胞IL-13R表达总评分≥4的比例明显高于正常对照和疾病对照。小管间质‘正常’的患者IL-13R表达总评分均≥4,分布于小管的基底和侧面细胞膜。小管间质急性病变患者IL-13R表达总评分≥4比例为88.9%,分布于基底和侧面细胞膜。小管间质急性+慢性病变患者IL-13R表达总评分≥4比例为50.0%,分布于基底和侧面细胞膜,以基底面为主。小管间质慢性病变患者IL-13R表达很少,IL-13R表达总评分均≤2,主要分布于基底面细胞膜。FSGS患者IL-13R高表达的小管上皮细胞同时表达趋化因子RANTES,而且上皮细胞标志物N-cadherin表达减少。结论:首次证实人肾活检组织近端小管上皮细胞表达IL-13R。FSGS患者近端小管上皮细胞IL-13R表达的范围和强度高于具有同等程度蛋白尿的IgAN和MN患者。FSGS患者小管IL-13R的表达范围和强度与肾小管病变性质相关。FSGS患者IL-13R的表达增强启动了小管上皮细胞的损伤过程。本研究表明,FSGS患者肾小管上皮细胞IL-13R高表达参与肾小管间质的损伤,而且有助于进一步探讨FSGS患者足细胞与肾小管上皮细胞损伤的共同分子基础。更多还原

【Abstract】 Objective:Although it is believed that FSGS is a disease of podocyte,tubular injury is a common phenomena in such patients,and the degree of proteinuria is insufficient to explain the reasons.It has been reported that IL-13 could lead to podocyte injury by IL-13 receptor(IL-13R) on podocyte.Since podocyte shares many common molecules with renal tubular cell,which become molecular basis mediating podocyte and renal tubular cell common injury.To answer this question,IL-13R expression in tubular cell was observed in the renal biopsy tissues from patients with FSGS.Methodology:Fourty-one patients with idiopathic FSGS diagnosed by renal biopsy was recruited in this study.The patients with IgA nephropathy(IgAN,n=11) and membranous nephropathy(MN,n=10) served as disease controls.Five donor kidneys served as normal controls.IL-13R and RANTES(regulated on activation normal T-cell expressed and secreted) expression and distribution in renal tissue were determined by immunofluorescence staining.Tubulointerstitial lesions in FSGS patients were classified into normal,acute lesion,acute/chronic lesion and chronic lesion.The distribution and intensity of IL-13R was evaluated by scoring method.Double staining of IL-13R/N-cadherin was performed to observe IL-13R distribution.Results:The trace expression of IL-13R was found in proximal tubular cells in normal controls.The distribution and intensity of IL-13R staining was higher in FSGS patients than that in normal controls,IgAN and MN.In addition,the maximum expression of IL-13R was found in FSGS patients with looks normal tubulointerstitium and those with acute tubulointerstitial lesion,the medium expression of IL-13R in those with acute /chronic tubulointerstitial lesion and minor expression of IL-13R in those with chronic tubulointerstitial lesion.The expression and distribution of RANTES was paralleled to that of IL-13R.Reduced expression of epithelial cell marker N-cadherin was observed in the tubular cells with high expression of IL-13R.Conclusion:IL-13R was expressed in normal human renal tubular cells.The patients with FSGS had wider and higher IL-13R expression than that other glomerular diseases with same degree of proteinuria.Tubular IL-13R distribution and intensity were different according to tubulointerstitial lesions in FSGS patients.Tubular IL-13R high expression may participate in tubular cell injury in FSGS patients.更多还原