Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea
Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea
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DOI：
10.1097/01.asn.0000067645.49562.09
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发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Haller, H
中科院分区：
文献类型：
--
作者：
Elger, M;Hentschel, H;Haller, H
哺乳动物肾脏对部分肾切除术的反应是肾小球和肾小管肥大，但没有肾脏再生。相比之下，已知低等脊椎动物中会发生肾再生。了解肾再生的潜在机制是非常重要的，然而，一个可用的动物模型尚未开发。在欧洲小斑点狗鲨Scyliorhinus caniculus（Hentschel H. Am J Anat 190：309-333，1991），以及多刺角鲨Squalus acanthias和小鳐Leucoraja erinacea。该区域的特点是生产新的肾单位，并配有逆流系统。为了进一步分析板鳃鱼类的肾发生区，建立了肾缩小模型。在成年的小溜冰鞋肾的肾发生区类似于胚胎后肾，并包含干细胞样间充质细胞，分支集合管系统的尖端，和动脉系统的生长。肾单位发育的四个阶段通过连续切片进行分析并定义：第一阶段，聚集的间充质细胞;第二阶段，具有高棱柱状上皮细胞的S形体状结构;第三阶段，节段性肾单位分离;第四阶段，功能性肾单位。分析肾部分切除术后的分期。此外，通过掺入溴脱氧尿苷（BrdU）来评估细胞增殖。在接受肾部分切除术的动物中产生了新的肾单位。在10周内，在残余组织和对侧肾中，在肾生成区中的生长被极大地刺激。与对照组相比，每个肾横截面的间充质细胞聚集体显著增加（第1阶段，0.64 +/- 0.28对0.27 +/- 0.25; P < 0.005; n = 10只动物/组）。S形体样囊肿的情况也是如此（II期，0.24 +/- 0.19对0.08 +/- 0.09; P < 0.02）。对侧肾的生肾区的细胞增殖也大大增强（每个横截面14.42 +/- 3.26 vs 2.64 +/- 1.08 BrdU阳性细胞，P < 0.001）。因此，旱冰鱼在其一生中具有一个含干细胞样间充质细胞的生肾区。肾部分切除术通过加速肾生成诱导肾生长。这种独特的模型可能有助于理解肾脏再生。
The mammalian kidney responds to partial nephrectomy with glomerular and tubular hypertrophy, but without renal regeneration. In contrast, renal regeneration in lower vertebrates is known to occur. Understanding the underlying mechanisms of renal regeneration is highly important; however, a serviceable animal model has not been developed. A neonephrogenic zone has been identified in the European lesser spotted dogfish, Scyliorhinus caniculus (Hentschel H. Am J Anat 190: 309-333, 1991), as well as in the spiny dogfish Squalus acanthias and the little skate, Leucoraja erinacea. The zone features the production of new nephrons complete with a countercurrent system. To analyze this nephrogenic region of elasmobranch fish further, a renal reduction model was established. The neonephrogenic zone in the adult kidney of the little skate resembles the embryonic metanephric kidney and contains stem cell-like mesenchymal cells, tips of the branching collecting duct system, and outgrowth of the arterial system. Four stages of nephron development were analyzed by serial sections and defined: stage I, aggregated mesenchymal cells; stage II, S-shaped body-like structure with high-prismatic epithelial cells; stage III, segmental nephron segregation; stage IV, functioning nephron. The stages were analyzed after partial nephrectomy. In addition, cell proliferation was assessed by incorporation of bromo-deoxyuridine (BrdU). New nephrons developed in animals undergoing partial nephrectomy. Growth was greatly stimulated in the nephrogenic zone, both in the remnant tissue and in the contralateral kidney within 10 wk. Mesenchymal cell aggregates increased significantly per renal cross-section compared with controls (stage 1, 0.64 +/- 0.28 versus 0.27 +/- 0.25; P < 0.005; n = 10 animals per group). The same was the case for S-shaped body-like cysts (stage II, 0.24 +/- 0.19 versus 0.08 +/- 0.09; P < 0.02). Cellular proliferation in the neonephrogenic zone of the contralateral kidney was also greatly enhanced (14.42 +/- 3.26 versus 2.64 +/- 1.08 BrdU-positive cells per cross-section, P < 0.001). It is concluded that the skate possesses a nephrogenic zone containing stem cell-like mesenchymal cells during its entire life. Partial nephrectomy induces renal growth by accelerating nephrogenesis. This unique model may facilitate understanding renal regeneration.