Asymmetric origins of the mature glomerular basement membrane.
Asymmetric origins of the mature glomerular basement membrane.
复制标题
成熟肾小球基底膜的不对称起源。
DOI：
10.1002/jcp.1041570122
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发表时间：
1993
影响因子：
5.6
通讯作者：
Lovett,DH
中科院分区：
文献类型：
--
作者：
Lee,LK;Pollock,AS;Lovett,DH
肾血浆滤过是一项重要的生理功能，它取决于肾小球基底膜（GBM）内细胞外基质蛋白的精确组成和排列。在肾胚胎发生过程中，由内皮细胞和内脏上皮细胞独立产生的离散基底膜融合而成的GBM，可能来自系膜细胞分泌的基质。然而，在成熟动物中，上皮细胞通常被认为是所有GBM成分蛋白的唯一来源。尽管组织化学技术已经确定了组成蛋白的最终结构和分布，但三种常驻肾小球细胞类型对成熟GBM的维持和更新的个体贡献仍然不确定。我们报道了一种新技术的应用，原位反转录（ISRT），定位九种主要GBM蛋白成分的RNA转录物在肾小球的密切相关的细胞。利用这种技术，我们发现在正常成年大鼠肾小球中，硫酸肝素蛋白聚糖和层粘胶蛋白S链的RNA转录本主要由内脏上皮细胞表达，而IV型α‐1和α‐2型胶原转录本则以异质模式局限于内皮细胞。所有三种肾小球细胞类型均表达肠动蛋白和层粘连蛋白- A和- B2链的RNA转录本，而层粘连蛋白- B1和纤维连接蛋白转录本仅限于系膜。这些发现表明，成熟动物的GBM合成并不局限于上皮细胞，所有固有的肾小球细胞都参与GBM蛋白成分的产生。ISRT技术还提供了额外的，意想不到的发现，在单个肾小球细胞类型中存在明显的合成异质性。©1993 Wiley‐Liss, Inc。
Renal plasma filtration is a critical physiologic function that depends upon the precise composition and arrangement of the constituent extracellular matrix proteins within the glomerular basement membrane (GBM). The GBM develops during renal embryogenesis by the fusion of discrete basement membranes produced independently by endothelial and visceral epithelial cells, and, possibly from matrix secreted by the mesangial cells. In the mature animal, however, the epithelial cell has generally been accepted as the sole source of all GBM constituent proteins. Although the final structures and distributions of the component proteins have been defined by histochemical techniques, the individual contributions of the three resident glomerular cell types to the maintenance and turnover of the mature GBM remain uncertain. We report the application of a new technique, in situ reverse transcription (ISRT), for the localization of RNA transcripts of nine major GBM protein components within the closely apposed cells of the glomerulus. Using this technique, we demonstrate that in normal adult rat glomeruli the RNA transcripts for heparan sulfate proteoglycan and the laminin‐S chain are primarily expressed by visceral epithelial cells, while Type IV α‐1 and α‐2 collagen transcripts were restricted to the endothelial cells in a heterogeneous pattern. RNA transcripts for entactin and the laminin‐A and ‐B2 chains were expressed by all three glomerular cell types, while laminin‐B1 and fibronectin transcripts were limited to the mesangium. These findings demonstrate that GBM synthesis in the mature animal is not restricted to the epithelial cell and that all intrinsic glomerular cells contribute to the production of GBM protein components. The ISRT technique also provided the additional, and unexpected, finding that appreciable synthetic heterogeneity exists within individual glomerular cell types. © 1993 Wiley‐Liss, Inc.