Genes that Confer the Identity of the Renin Cell

Genes that Confer the Identity of the Renin Cell
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DOI:
10.1681/asn.2011040401
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发表时间:
2011-12-01
影响因子:
13.6
通讯作者:
Gomez, R. Ariel
Gomez, R. Ariel
中科院分区:
医学1区
文献类型:
--
作者:
Brunskill, Eric W.;Sequeira-Lopez, Maria Luisa S.;Gomez, R. Ariel

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肾素表达细胞调节血压、体液-电解质稳态和肾脏发育,但对控制这些细胞身份的遗传调控网络知之甚少。在这里,我们比较了肾素细胞与肾脏中大多数细胞在不同发育阶段的基因表达谱,以及在已知的生理挑战诱导小动脉平滑肌细胞转化为肾素表达细胞后的基因表达谱。在所有阶段,肾素细胞表达一组独特的肾素表型特征基因,这与肾脏中的其他细胞类型有很大不同。例如,肾素表型的细胞表达Akr1b7,成熟细胞表达肾脉管系统发育所需的血管生成因子和RGS (g蛋白信号调节因子)基因,这表明肾素细胞和周细胞之间存在潜在的关系。与肾小球上游的小动脉平滑肌细胞在生理应激下可在成人体内短暂获得胚胎表型的可塑性相反,成人肾小球旁细胞始终同时具有平滑肌细胞和肾素细胞的特征。综上所述,这些结果确定了肾素表达细胞在不同成熟阶段的基因表达谱,并表明肾小球旁细胞保持了平滑肌和肾素表达细胞的特性,可能通过收缩和内分泌功能快速控制体液和血压。
Renin-expressing cells modulate BP, fluid-electrolyte homeostasis, and kidney development, but remarkably little is known regarding the genetic regulatory network that governs the identity of these cells. Here we compared the gene expression profiles of renin cells with most cells in the kidney at various stages of development as well as after a physiologic challenge known to induce the transformation of arteriolar smooth muscle cells into renin-expressing cells. At all stages, renin cells expressed a distinct set of genes characteristic of the renin phenotype, which was vastly different from other cell types in the kidney. For example, cells programmed to exhibit the renin phenotype expressed Akr1b7, and maturing cells expressed angiogenic factors necessary for the development of the kidney vasculature and RGS (regulator of G-protein signaling) genes, suggesting a potential relationship between renin cells and pericytes. Contrary to the plasticity of arteriolar smooth muscle cells upstream from the glomerulus, which can transiently acquire the embryonic phenotype in the adult under physiologic stress, the adult juxtaglomerular cell always possessed characteristics of both smooth muscle and renin cells. Taken together, these results identify the gene expression profile of renin-expressing cells at various stages of maturity, and suggest that juxtaglomerular cells maintain properties of both smooth muscle and renin-expressing cells, likely to allow the rapid control of body fluids and BP through both contractile and endocrine functions.