一个完整的人单克隆抗体(CR002)标识PDGF-D mesangioproliferative肾小球肾炎的一种新的中介。

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Ostendorf T, van Roeyen CR,彼得森JD Kunter U, F,靠自己去哈马德AJ,陈G,贾XC,时J, Gazit-Bornstein G, Keyt英航Lichenstein HS, LaRochelle WJ Floege J

一个完整的人单克隆抗体(CR002)标识PDGF-D mesangioproliferative肾小球肾炎的一种新的中介。

J是Soc Nephrol。2003年9月,14日(9):2237 - 47。

PubMed ID

12937299 (在PubMed

]

文摘

PDGF-B mesangioproliferative疾病的重要性。PDGF-D, PDGF同种型PDGF-B一样,通过PDGF betabeta-receptor信号。本研究首先确定PDGF-D对大鼠系膜细胞和促有丝分裂的不是PDGF-B拮抗剂抑制。低水平的PDGF-D信使rna检测正常大鼠肾小球。后感应anti-Thy 1.1马伯,mesangioproliferative肾炎大鼠的肾小球PDGF-D mRNA和蛋白表达显著增加天4 - 9与nonnephritic老鼠相比。峰PDGF-D mRNA的表达比峰值晚发生2 d PDGF-B mRNA的表达。此外,PDGF-D血清水平显著增加肾脏的动物在7天。调查PDGF-D的功能作用,中和完全人类使用XenoMouse马伯生成技术。老鼠全身的1.1 anti-Thy肾炎治疗与不同数量的天3和5完全人类PDGF-DD-specific中和马伯(CR002)等量的马伯无关的控制,或由腹腔内注射PBS。具体PDGF-D拮抗作用导致剂量依赖性(67%)减少肾小球细胞增殖。 As judged by double immunostaining for 5-bromo-2'-deoxyuridine and alpha-smooth muscle actin, glomerular mesangial cell proliferation was reduced by up to 57%. Reduction of glomerular cell proliferation in the rats that received CR002 was not associated with reduced glomerular expression of PDGF-B mRNA. PDGF-D antagonism also led to reduced glomerular infiltration of monocytes/macrophages (day 5) and reduced accumulation of fibronectin (day 8). In contrast, no effect was noted in normal rats that received an injection of CR002. These data show that PDGF-D is overexpressed in mesangioproliferative states and can act as an auto-, para-, or even endocrine glomerular cell mitogen, indicating that antagonism of PDGF-D may represent a novel therapeutic approach to mesangioproliferative glomerulonephritides.

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药物

CR002