Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells
Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells
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DOI：
10.1016/s0002-9440(10)63868-0
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发表时间：
2003-03-01
影响因子：
6
通讯作者：
Betsholtz, C
中科院分区：
文献类型：
--
作者：
Bondjers, C;Kalén, M;Betsholtz, C
所有的毛细血管都由内皮管组成，周围环绕着被称为周细胞的壁细胞。周细胞的起源、募集和功能知之甚少，但这些细胞的重要性在缺乏调控周细胞募集到胚胎血管的因子的小鼠的严重心血管缺陷以及糖尿病的周细胞丢失和微血管病变之间的关联中得到了强调。周细胞研究中的一个普遍问题是缺乏这些细胞的标志物。为了确定周细胞的新标记物，我们利用了血小板衍生生长因子(PDGF)-B基因敲除小鼠模型，在该模型中，中枢神经系统发育中的血管几乎完全没有周细胞。利用基因芯片技术，分析PDGF-B缺失胚胎与野生型胚胎的基因表达差异，寻找下调基因。我们的芯片中下调最多的基因是RGS5，它是G蛋白的GTPase激活蛋白RGS家族的成员。原位杂交发现RGS5在脑周细胞中表达，在某些其他部位的周细胞和血管平滑肌细胞中也有表达。PDGF-B和PDGFRβ缺失胚胎中RGS5的表达缺失与这些小鼠的周细胞丢失有关。RGS5在罕见的周细胞中的残留表达表明，RGS5是一种独立于PDGF-B/Rbeta信号表达的周细胞标志物。以RGS5作为验证原则，我们的数据证明了对小鼠周细胞发育异常模型的微阵列分析在识别新的周细胞特异性标记方面的有效性。
All blood capillaries consist of endothelial tubes surrounded by mural cells referred to as pericytes. The origin, recruitment, and function of the pericytes is poorly understood, but the importance of these cells is underscored by the severe cardiovascular defects in mice genetically devoid of factors regulating pericyte recruitment to embryonic vessels, and by the association between pericyte loss and microangiopathy in diabetes mellitus. A general problem in the study of pericytes is the shortage of markers for these cells. To identify new markers for pericytes, we have taken advantage of the platelet-derived growth factor (PDGF)-B knockout mouse model, in which developing blood vessels in the central nervous system are almost completely devoid of pericytes. Using cDNA microarrays, we analyzed the gene expression in PDGF-B null embryos in comparison with corresponding wild-type embryos and searched for downregulated genes. The most down-regulated gene present on our microarray was RGS5, a member of the RGS family of GTPase-activating proteins for G proteins. In situ hybridization identified RGS5 expression in brain pericytes, and in pericytes and vascular smooth muscle cells in certain other, but not all, locations. Absence of RGS5 expression in PDGF-B and PDGFRbeta-null embryos correlated with pericyte loss in these mice. Residual RGS5 expression in rare pericytes suggested that RGS5 is a pericyte marker expressed independently of PDGF-B/Rbeta signaling. With RGS5 as a proof-of-principle, our data demonstrate the usefulness of microarray analysis of mouse models for abnormal pericyte development in the identification of new pericyte-specific markers.