Oliver J A, Al-Awqati Q
Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, New York 10032, USA.
J Clin Invest. 1998 Sep 15;102(6):1208-19. doi: 10.1172/JCI785.
In the kidney, there is a close and intricate association between epithelial and endothelial cells, suggesting that a complex reciprocal interaction may exist between these two cell types during renal ontogeny. Thus, we examined whether metanephrogenic mesenchymal cells secrete endothelial mitogens. With an endothelial mitogenic assay and sequential chromatography of the proteins in the media conditioned by a cell line of rat metanephrogenic mesenchymal cells (7.1.1 cells), we isolated a protein whose amino acid analysis identified it as hepatoma-derived growth factor (HDGF). Media conditioned with Cos-7 cell transfected with HDGF cDNA stimulated endothelial DNA synthesis. With immunoaffinity purified antipeptide antibodies, we found that HDGF was widely distributed in the renal anlage at early stages of development but soon concentrated at sites of active morphogenesis and, except for some renal tubules, disappeared from the adult kidney. From a 7.1.1 cells cDNA library, a clone of most of the translatable region of HDGF was obtained and used to synthesize digoxigenin-labeled riboprobes. In situ hybridization showed that during kidney development mRNA for HDGF was most abundant at sites of nephron morphogenesis and in ureteric bud cells while in the adult kidney transcripts disappeared except for a small population of distal tubules. Thus, HDGF is an endothelial mitogen that is present in embryonic kidney, and its expression is synchronous with nephrogenesis.
在肾脏中，上皮细胞与内皮细胞之间存在着紧密而复杂的联系，这表明在肾脏发育过程中这两种细胞类型之间可能存在复杂的相互作用。因此，我们研究了后肾间充质细胞是否分泌内皮细胞有丝分裂原。通过内皮细胞有丝分裂原检测以及对大鼠后肾间充质细胞系（7.1.1细胞）条件培养基中的蛋白质进行连续层析，我们分离出一种蛋白质，其氨基酸分析确定它为肝癌衍生生长因子（HDGF）。用HDGF cDNA转染的Cos-7细胞的条件培养基刺激内皮细胞DNA合成。利用免疫亲和纯化的抗肽抗体，我们发现HDGF在发育早期广泛分布于肾脏原基，但很快集中在活跃形态发生部位，并且除了一些肾小管外，在成年肾脏中消失。从7.1.1细胞cDNA文库中获得了HDGF大部分可翻译区域的克隆，并用于合成地高辛标记的核糖探针。原位杂交显示，在肾脏发育过程中，HDGF的mRNA在肾单位形态发生部位和输尿管芽细胞中最为丰富，而在成年肾脏中，除了一小部分远端小管外，转录本消失。因此，HDGF是一种存在于胚胎肾脏中的内皮细胞有丝分裂原，其表达与肾发生同步。
