Podocyte Repopulation Contributes to Regression of Glomerular Injury Induced by Ace Inhibition
Podocyte Repopulation Contributes to Regression of Glomerular Injury Induced by Ace Inhibition
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DOI：
10.2353/ajpath.2009.080227
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发表时间：
2009-03-01
影响因子：
6
通讯作者：
Remuzzi, Andrea
中科院分区：
文献类型：
--
作者：
Macconi, Daniela;Sangalli, Fabio;Remuzzi, Andrea
血管紧张素转换酶（ACE）抑制诱导慕尼黑Wistar Fromter（MWF）大鼠（一种自发性肾小球损伤模型）的肾小球修复。在这项研究中，我们调查了这种影响是否与肾小球细胞数量的变化有关，特别是足细胞，随着年龄的增长而逐渐减少。在40周和观察20周后，对患有晚期肾病的MWF大鼠进行了研究，无论是否使用ACE抑制剂赖诺普利治疗。40周龄Wistar大鼠作为对照。在未经治疗的MWF大鼠中，蛋白尿、高血压、肾小球硬化和肾功能恶化，而赖诺普利引起功能和结构变化的消退。尽管未治疗的MWF大鼠肾小球细胞过多，但每个肾小球的内皮细胞数量没有变化，足细胞数量甚至减少。ACE抑制剂阻止了肾小球细胞数量的进行性增加，并增强了内皮细胞体积密度。令人惊讶的是，赖诺普利不仅阻止了年龄相关的足细胞损失，而且还增加了肾小球足细胞的数量超过基线，这与增殖的Wilms肿瘤1阳性细胞数量增加，细胞周期蛋白依赖性激酶抑制剂p27表达丧失和壁足细胞数量增加有关。这些数据表明ACE抑制主要通过恢复该肾小球损伤模型中的足细胞群来重建肾小球毛细血管。赖诺普利治疗的MWF大鼠中壁足细胞数量增加表明Bowman囊上皮细胞的重塑有助于这种效应。(Am J Pathol 2009，174：797-807; DOI：10.2353/ajpath.2009.080227）
Angiotensin-converthig enzyme (ACE) inhibition induces glomerular repair in the Munich Wistar Fromter (MWF) rat, a model of spontaneous glomerular injury. In this study, we investigated whether this effect is related to changes In glomerular cell number, particularly of podocytes, which are progressively lost with age. MWF rats with advanced nephropathy were studied at both 40 weeks and after 20 weeks of observation either with or without treatment with the ACE inhibitor lisinoprill. Forty-week-old Wistar rats were used as controls. In untreated MWF rats, proteinuria, hypertension, glomerulosclerosis, and renal function worsened, while lisinopril induced regression of both functional and structural changes. Despite glomerular hypercellularity in untreated MWF rats, the number of endothelial cells per glomerulus did not change, and podocyte number even decreased. ACE inhibition halted the progressive increase in glomerular cell number and enhanced endothelial cell volume density. Surprisingly, lisinopril not only halted age-related podocyte loss but also increased the number of glomerular podocytes above baseline, which was associated with an Increased number of proliferating Wilms tumor 1-positive cells, loss of cyclin-dependent kinase inhibitor p27 expression, and increased number of parietal podocytes. These data indicate that ACE inhibition restructures glomerular capillary, primarily by restoring the podocyte population in this model of glomerular injury. Increased parietal podocyte number in lisinopril-treated MWF rats suggests that the remodeling of Bowman's capsule epithelial cells contributes to this effect. (Am J Pathol 2009, 174:797-807; DOI: 10.2353/ajpath.2009.080227)