Development of the renin-expressing cell

肾素表达细胞的发育

• 批准号: 7996188
• 负责人: MARIA LUISA Soledad SEQUEIRA-LOPEZ
• 金额: $ 5.4万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7996188
• 关键词: Address; Adrenal Medulla; Adult; Cartilage; Cell Lineage; Cells; Characteristics; Congenital Abnormality; Development; Ectoderm; Electrolytes; Embryo; Epidermis; Generations; Genes; Head; Homeostasis; Hormones; Kidney; Kidney Diseases; Knowledge; Life; Liquid substance; Mesoderm; Molecular; Mus; Neural Crest; Neural Crest Cell; Neuroectoderm; Prevention; Renin; Role; Skin; Structure of choroid plexus; Sympathetic Ganglia; Tissues; Work; blood pressure regulation; cell type; hypertension treatment; mouse model; nestin protein; precursor cell; recombinase; relating to nervous system; tool

DESCRIPTION (provided by applicant): Renin-synthesizing cells are known to be crucial in the regulation of blood pressure and fluid and electrolyte homeostasis. These cells have been considered as terminally differentiated because they synthesize a hormone (renin), are few in numbers, and are restricted to a juxtaglomerular localization in the adult mammalian kidney. Recently, however, we showed that renin cells are precursors for multiple renal and extrarenal cell types. Although it has been accepted that renin cells derive from the mesoderm, our preliminary work indicates that either a subset or all of the renin-expressing cells may derive from ectoderm. We further hypothesize that renin is necessary for the differentiation of ectodermal precursors into their derivative tissues (i.e. skin, choroid plexus, sympathetic ganglia, adrenal medulla and head cartilage). To define whether renin-expressing cells derive from neuroectodermal or neural crest cells we will use available mouse models that mark cells derived from the neuroectoderm, the neural crest and the renin cell lineage. To determine whether deletion of the renin gene in neuroectodermal/neural crest/ epidermal precursors results in defective development of their derivative tissues, we will generate a renin-floxed mouse and will cross it with mice expressing ere recombinase in precursors of neuroectoderm (nestin-cre), neural crest cells (wnt1-cre) and epidermis (K14-cre). The proposed studies should generate fundamental new knowledge on renin cell specification and neural/ectodermal development. Furthermore, the generation of a renin-floxed mouse will be a valuable tool to solve the long standing controversy regarding the role of locally generated renin versus circulating renin. This work has the potential to open new avenues for the understanding, prevention and treatment of hypertension, birth defects and kidney diseases.

描述（由申请人提供）： 已知合成肾素的细胞在调节血压以及液体和电解质稳态中至关重要。这些细胞被认为是终末分化的，因为它们合成激素（肾素），数量很少，并且局限于成年哺乳动物肾脏中的肾小球定位。然而，最近，我们发现，肾素细胞的前体多种肾脏和肾外细胞类型。虽然它已被接受，肾素细胞来自中胚层，我们的初步工作表明，无论是一个子集或所有的肾素表达细胞可能来自外胚层。我们进一步假设，肾素是必要的外胚层前体分化成其衍生组织（即皮肤，脉络丛，交感神经节，肾上腺髓质和头部软骨）。为了确定表达肾素的细胞是否来源于神经外胚层或神经嵴细胞，我们将使用标记来源于神经外胚层、神经嵴和肾素细胞谱系的细胞的可用小鼠模型。为了确定神经外胚层/神经嵴/表皮前体中的肾素基因的缺失是否导致其衍生组织的发育缺陷，我们将产生一只肾素-floxed小鼠，并将其与在神经外胚层（nestin-cre）、神经嵴细胞（wnt 1-cre）和表皮（K14-cre）的前体中表达ere重组酶的小鼠杂交。 拟议的研究应产生关于肾素细胞规格和神经/外胚层发育的基本新知识。此外，产生的肾素-floxed小鼠将是一个有价值的工具，以解决长期存在的争议，局部产生的肾素与循环肾素的作用。这项工作有可能为理解、预防和治疗高血压、出生缺陷和肾脏疾病开辟新的途径。

项目成果

Histone acetyl transferases CBP and p300 are necessary for maintenance of renin cell identity and transformation of smooth muscle cells to the renin phenotype.

• DOI: 10.1152/ajpheart.00782.2011
• 发表时间: 2012-06
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: E. Pentz;Magali Cordaillat;Oscar A. Carretero;Ana E. Tucker;M. S. Sequeira Lopez;R. A. Gomez

Who and where is the renal baroreceptor?: the connexin hypothesis.

• DOI: 10.1038/ki.2008.536
• 发表时间: 2009-03
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Gomez, R. Ariel;Lopez, Maria Luisa S. Sequeira
• 通讯作者: Lopez, Maria Luisa S. Sequeira

Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension.

• DOI: 10.1038/ki.2010.257
• 发表时间: 2010-10
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Wagner, Charlotte;Jobs, Alexander;Schweda, Frank;Kurtz, Lisa;Kurt, Birguel;Lopez, Maria L. Sequeira;Gomez, R. Ariel;Van Veen, Toon A. B.;De Wit, Cor;Kurtz, Armin
• 通讯作者: Kurtz, Armin