肥大细胞、干细胞因子和蛋白酶激活受体-2在 IgA 肾病小管间质病变中的作用。
Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy.
机构信息
Nephrology Institute of Central South University, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
出版信息
Inflamm Res. 2010 Jul;59(7):551-9. doi: 10.1007/s00011-010-0159-7. Epub 2010 Feb 4.
BACKGROUND
To elucidate the role of mast cells (MCs) in the pathogenesis of tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy specimens and serum creatinine levels, urinary protein excretion in patients with IgA nephropathy.
METHODS
Thirty-five patients with IgA nephropathy were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining. Monoclonal antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2 were used as primary antibodies. Ten cortical interstitial fields were randomly selected and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields.
RESULTS
In all of the control subjects, few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were positively correlated with the degree of interstitial fibrosis. A close correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha-SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a significant positive correlation was observed between the number of interstitial MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum creatinine level (r = 0.738 for MCs, r = 0.658 for alpha-SMA, r = 0.692 for PAR-2, r = 0.754 for SCF, P < 0.05).
CONCLUSIONS
Our findings suggest that MC infiltration possibly induced by SCF in renal interstitial tissues seems to be associated with tubulointerstitial fibrosis through PAR-2 in IgA nephropathy.
背景
为了阐明肥大细胞（MCs）在 IgA 肾病（IgAN）肾小管间质病变发病机制中的作用，我们研究了 MC 数量、血清干细胞因子（SCF）、蛋白酶激活受体-2（PAR-2）和α-平滑肌肌动蛋白（α-SMA）在肾脏中的表达，以及 MC 数量、SCF、PAR-2、α-SMA 与活检标本中肾小管间质病变和血清肌酐水平、IgA 肾病患者尿蛋白排泄之间的相关性。
方法
本研究纳入 35 例 IgA 肾病患者。每位患者在活检时均获得血清肌酐和尿蛋白排泄等临床参数。使用石蜡包埋切片进行免疫组织化学染色。使用针对人胰蛋白酶、α-SMA 和 SCF 的单克隆抗体和针对 PAR-2 的多克隆抗体作为初级抗体。随机选择 10 个皮质间质场并用计算机辅助彩色图像分析仪进行评估。肾小管间质纤维化通过 Masson 三色染色评估的 10 个皮质间质场中的面积百分比进行评估。
结果
在所有对照组中，肾小球和间质中仅观察到少量胰蛋白酶阳性 MC。相比之下，病变肾脏的间质中仅观察到稀疏的 MC，而肾小球中则没有。肾小管间质病变中间质 MC 的数量、SCF、PAR-2 和 α-SMA 的表达与间质纤维化程度呈正相关。MC、α-SMA、PAR-2 和 SCF 之间存在密切相关性（α-SMA 为 r = 0.887，PAR-2 为 r = 0.844，SCF 为 r = 0.853，P < 0.01）。此外，α-SMA、PAR-2 和 SCF 之间也存在密切相关性（PAR-2 为 r = 0.874，SCF 为 r = 0.862，P < 0.01）。PAR-2 与 SCF 相关（r = 0.893，P < 0.01）。此外，间质 MC 数量、SCF、PAR-2 和 α-SMA 的表达与血清肌酐水平呈显著正相关（MC 为 r = 0.738，α-SMA 为 r = 0.658，PAR-2 为 r = 0.692，SCF 为 r = 0.754，P < 0.05）。
结论
我们的研究结果表明，IgA 肾病中肾间质组织中可能由 SCF 诱导的 MC 浸润似乎通过 PAR-2 与肾小管间质纤维化有关。
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