Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy

Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy
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DOI:
10.1038/ki.1997.37
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发表时间:
1997-01-01
影响因子:
19.6
通讯作者:
Osawa, G
Osawa, G
中科院分区:
医学1区
文献类型:
--
作者:
Sasaki, T;Jyo, Y;Osawa, G

文献摘要

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在本研究中,两个系列的实验进行了PAN肾病大鼠给予成纤维细胞生长因子2(FGF?)或FGF2中和抗体。在第一系列实验中,在PAN注射后施用10 μ g剂量的FGF 2(FGF 2组)、40 μ g剂量的FGF 2中和抗体(抗FGF 2组)或等体积的生理盐水(对照组)持续4天。FGF2组尿蛋白增加明显高于其他两组。PCNA(+)肾小球细胞在FGF 2组、对照组和抗FGF 2组中以降序发现。PCNA阳性细胞主要为足细胞和Bowman囊上皮细胞。在抗FGF2组中,足细胞损伤的标志物结蛋白的染色显著减少。在FGF 2组、对照组和抗FGF 2组中,发现肾小球粘连性病变以降序排列。第二系列实验设计为研究FGF2中和抗体(40 μ g,在PAN注射后5天,在MoAb组中)对PAN肾病大鼠中由重复(两个疗程)注射引起的严重损伤的足细胞的作用。结果与系列1相同。两组尿蛋白排泄量均增加,但在第40天,MoAb组的尿蛋白水平突然下降。观察到与IgG组(施用小鼠IgG)相比,MoAb组具有很少的粘附肾小球,并且Bowman囊的PCNA(+)上皮细胞也很少。推测FGF2可能通过刺激足细胞和Bowman囊上皮细胞的增殖而促进粘连性病变的形成。此外,由于结蛋白评分和蛋白尿增加,认为FGF 2本身损害足细胞。
In the present study, two series of experiments were done with PAN nephropathy rats given fibroblast growth factor 2 (FGF?) or FGF2 neutralizing antibodies. Ln the first series of experiments, a dose of 10 mu g of FGF2 (FGF2 group), 40 mu g of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume of physiological saline (Control group) was administered for four days after PAN injection. Urinary protein increased more in the FGF2 group than in the other two groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2, Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were found in decreasing order in groups FGF2, Control and Anti-FGF2. The second series of experiments was designed to study the effects of FGF2 neutralizing antibody (40 mu g for 5 days after PAN injection, in MoAb group) on severely damaged podocytes caused by repeated (two courses) injections in the PAN nephropathy rats. The results were the same as those in series 1. An increase in urinary protein excretion was observed in both groups, but on the 40th day, the level of proteinuria in the MoAb group decreased abruptly. It was observed that the MoAb group had few adhesive glomeruli compared to the IgG group (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's capsule were also few. It was supposed that FGF2 would promote the formation of adhesive lesions by stimulating the proliferation of podocytes and epithelial cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair podocytes because of the increasing desmin score and proteinuria.