THE COMPLEMENTARY DEOXYRIBONUCLEIC-ACID SEQUENCE, TISSUE DISTRIBUTION, AND CELLULAR-LOCALIZATION OF THE RAT GRANULIN PRECURSOR
THE COMPLEMENTARY DEOXYRIBONUCLEIC-ACID SEQUENCE, TISSUE DISTRIBUTION, AND CELLULAR-LOCALIZATION OF THE RAT GRANULIN PRECURSOR
复制标题
DOI：
10.1210/en.133.6.2682
复制
发表时间：
1993-12-01
期刊：
影响因子：
4.8
通讯作者：
BATEMAN, A
中科院分区：
文献类型：
--
作者：
BHANDARI, V;GIAID, A;BATEMAN, A
颗粒蛋白(Granulins，GRN；又称上皮素)是一类富含半胱氨酸的多肽，在体外对上皮细胞的生长具有多效性。GRN/epi基因在上皮细胞系中广泛表达，其中许多细胞对基因产物产生反应，增加了自分泌或旁分泌调节的可能性。在体外，GRN基因在不同谱系的细胞类型中表达，包括上皮细胞、淋巴和髓系细胞以及成纤维细胞，但尚不清楚体内哪些细胞表达该基因。为了了解GRN基因产物的生理作用，有必要了解GRN基因在体内表达的背景。我们分离了大鼠GRN前体互补DNA，并通过Northern印迹分析和原位杂交检测了GRN基因表达的组织分布和细胞定位。互补DNA预测了一个由589个氨基酸组成的M(R)63,500蛋白，其中7个半GRN重复序列串联排列，与人类程序的总体同源性为75%。GRN基因在来自所有三个胚胎胚层的各种组织中都有表达，但在脾和几个具有内分泌意义的组织中含量最高，包括肾上腺、附睾腺、胎盘和卵巢。虽然基因在组织中广泛表达，但基因的表达仅限于特定的细胞类型。例如，在肾脏中，GRN信使RNA在近曲小管和远曲小管和Bowman囊上皮细胞中检测到，但在髓质上皮细胞中未检测到。在脾中，GRN信使RNA的表达定位于淋巴细胞，而杂交信号则在肝中散在分布的肝细胞中检测到。因此，虽然GRN基因在体外广泛表达于许多谱系的组织和细胞系中，但其原位表达仅限于造血细胞和一些上皮细胞。有限的细胞分布表明，GRN基因的表达在体内比在细胞培养中受到更密切的调控。它在原位上皮细胞的定位支持这些因子的自分泌或旁分泌作用。
Granulins (grns; also called epithelins) are cysteine-rich polypeptides with pleiotropic effects on epithelial cell growth in vitro. The grn/epi gene is widely expressed in epithelial cell lines, many of which respond to the gene product, raising the possibility of autocrine or paracrine regulation. In vitro the grn gene is expressed in cell types of diverse lineages, including epithelial cells, lymphoid and myeloid cells, and fibroblasts, but it is not known which cells express the gene in vivo. To understand the physiological role of the grn gene products it is necessary to know the context of grn gene expression in vivo. We have isolated the rat grn precursor complementary DNA and determined, by Northern blot analysis and in situ hybridization, the tissue distribution and cellular localization of grn gene expression. The complementary DNA predicts a 589-amino acid protein of M(r) 63,500 with seven and one-half grn repeats arranged in tandem and shows an overall identity of 75% with human progrn. The grn gene is expressed in a variety of tissues derived from all three embryonic germ layers but is most abundant in the spleen and several tissues of endocrine significance including the adrenal glands, epididymis, placenta, and ovary. Although widely expressed in tissues, gene expression is restricted to specific cell types. For example in the kidney, grn messenger RNA was detected in epithelial cells of the proximal and distal convoluted tubules and Bowman's capsule but not in medullary epithelia. In the spleen, grn messenger RNA expression was localized in lymphocytes, whereas hybridization signals were detected over scattered hepatocytes in the liver. Thus, although the grn gene is widely expressed in tissues and cell lines of many lineages in vitro, its expression in situ is restricted to hematopoietic and some epithelial cells. The restricted cell distribution suggests that the expression of the grn gene is more closely regulated in vivo than in cell cultures. Its localization to epithelial cells in situ supports an autocrine or paracrine role for these factors.