INSERM, U858/I2MR, Department of Renal and Cardiac Remodeling, Team 5, 31432 Toulouse Cedex 4, France.
J Am Soc Nephrol. 2010 Jul;21(7):1157-64. doi: 10.1681/ASN.2009090887. Epub 2010 May 6.
Severe inflammation characterizes rapidly progressive glomerulonephritides, and expression of the kinin B1 receptor (B1R) associates with inflammation. Delayed B1R blockade reduces renal inflammation in a model of unilateral ureteral obstruction, but whether B1R modulates the pathophysiology of glomerulonephritides is unknown. Here, we observed an association of B1R protein expression and inflammation, in both glomeruli and the renal interstitium, in biopsies of patients with glomerulonephritides, Henoch-Schönlein purpura nephropathy, and ANCA-associated vasculitis. In the nephrotoxic serum-induced glomerulonephritis model, we observed upregulation of the B1R receptor; treatment with a B1R antagonist beginning 2 weeks after the onset of disease reduced both glomerular and tubular lesions and improved renal function. B1R blockade reduced renal chemokine expression and macrophage accumulation. Collectively, our data demonstrate that blockade of the kinin B1R has significant potential for the treatment of glomerulonephritis.
严重炎症是快速进行性肾小球肾炎的特征，激肽 B1 受体（B1R）的表达与炎症有关。在单侧输尿管梗阻模型中，延迟 B1R 阻断可减少肾脏炎症，但 B1R 是否调节肾小球肾炎的病理生理学尚不清楚。在这里，我们观察到肾小球肾炎、过敏性紫癜性肾炎和 ANCA 相关性血管炎患者活检中 B1R 蛋白表达与炎症之间存在关联，在肾毒性血清诱导的肾小球肾炎模型中，我们观察到 B1R 受体的上调；从疾病开始后 2 周开始用 B1R 拮抗剂治疗可减少肾小球和肾小管损伤并改善肾功能。B1R 阻断减少了肾脏趋化因子的表达和巨噬细胞的积累。总的来说，我们的数据表明，阻断激肽 B1R 具有治疗肾小球肾炎的巨大潜力。
