Sox6 Role in Renin Expression During Juxtaglomerular Cells Expansion

Sox6 在肾小球旁细胞扩增过程中肾素表达中的作用

• 批准号: 10393935
• 负责人: Jose A. Gomez
• 金额: $ 4.43万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2023-01-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393935
• 关键词: Adult; Affect; American; Angiotensin I; Angiotensinogen; Angiotensins; Binding; Blood Pressure; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Career Mobility; Cell Differentiation process; Cells; Clinical; Clinical Pharmacology; Collaborations; Cyclic AMP; Data; Development; Dinoprostone; Disease; Down-Regulation; Environment; Faculty; Funding; Genetic Transcription; Heart failure; Homeostasis; Human; Hypertension; In Vitro; Juxtaglomerular Cell; Kidney; Knock-out; Laboratories; Lead; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Mesenchymal Differentiation; Microarray Analysis; Molecular; Mus; Myocardial Infarction; Organ; Pathway interactions; Patients; Peripheral Vascular Diseases; Pharmacology; Physiology; Play; Population; Postdoctoral Fellow; Process; Program Development; Proto-Oncogene Protein c-kit; Recovery; Renin; Research; Research Personnel; Role; SOX6 gene; Scheme; Single Nucleotide Polymorphism; Smooth Muscle Myocytes; Sodium; Stress; System; Testing; Time; TimeLine; Tissues; Training; Training Activity; Training Programs; Transgenic Mice; United States; Universities; WFDC2 gene; Work; adult stem cell; arteriole; blood pressure regulation; cardiac regeneration; career development; cell fate specification; experience; in vivo; instructor; interest; knock-down; member; mesenchymal stromal cell; novel; novel therapeutics; promoter; recruit; response; stem; stem cell differentiation; stem cells; stroke risk

PROJECT SUMMARY This proposal details a five-year mentored training program for the career development and advancement of Dr. Jose A. Gomez, into an independent investigator. Dr. Gomez is a Research Instructor in the Division of Clinical Pharmacology at Vanderbilt University. He graduated with a Doctorate in Pharmacology from Case Western Reserve University. In 2009, he joined Dr. Victor J. Dzau's laboratory as a Post-Doctoral Fellow at Duke University, and became interested in blood pressure control and hypertension. He joined Vanderbilt University as Research Instructor in the Department of Medicine/Division of Clinical Pharmacology in 2015. During his K01 award, he will work with Dr. Harrison in close collaboration with Dr. Pozzi and Dr. Harris. As a postdoctoral fellow he defined the role of renal mesenchymal stromal cells in blood pressure homeostasis. He found that adult kidney stem/progenitor cells have the capacity to differentiate into JG-like cells and/or contribute to JG cell expansion. In a second project he contributed to a study that found that renal MSCs are recruited via the Cox2-PGE2-EP4 pathway. He aslo investigated the mechanisms by which adult stem cells differentiate into specialized tissues, and determined that Sfrp2 plays an essential role in cardiac regeneration by promoting the differentiation of c-Kit+ cardiac progenitor cells to cardiomyocytes. Now as a Clinical Instructor in Vanderbilt University, under the mentorship of Dr. David Harrison, he is elucidating the transcriptional regulators that play a role in the programming of renal progenitor cells into Juxtaglomerular cells. He found that Sox6 is expressed in renin producing cells in the developing kidney and in the adult kidney after stimulation that promotes JG cell expansion. This suggests a novel role for Sox6 in renin cell fate specification and thereby in renal development and physiology. His preliminary data shows that Sox6 is required in the conversion of renal MSCs to renin expressing cells in vitro. In this K01 proposal, he will characterize a new key function of Sox6 in blood pressure homeostasis and Juxtaglomerular cell fate. The studies proposed in this K01, aim at identifying the mechanisms by which Sox6 plays a role in blood pressure homeostasis, and will open new opportunities for the therapy of hypertension. During his planned research, Dr. Gomez will become experienced in in vitro and in vivo approaches to study hypertension. In addition, his training plan includes didactic courses, seminars, and participation in career development programs at Vanderbilt that promote the retention and tenure of junior faculty members. Dr. Harrison and Dr. Gomez have developed a timeline for his career development and training activities that will enable him to compete for funding and to develop into an independent investigator in the field hypertension. 100% of his time will be protected for activities directly related to his career development. Vanderbilt University's research and academic environment is highly exceptional for trainee career development.

项目概要 该提案详细介绍了一项为期五年的指导培训计划，旨在促进职业发展和进步 Jose A. Gomez 博士成为一名独立调查员。戈麦斯博士是以下部门的研究讲师 范德比尔特大学临床药理学。他毕业于凯斯大学，获得药理学博士学位 西储大学。 2009年，他加入Victor J. Dzau博士实验室，担任博士后研究员。 杜克大学，并对血压控制和高血压产生了兴趣。他加入了范德比尔特 2015年担任大学医学系/临床药理学部研究讲师。 在获得 K01 奖项期间，他将与哈里森博士、波齐博士和哈里斯博士密切合作。 作为博士后研究员，他定义了肾间充质基质细胞在血压中的作用 体内平衡。他发现成体肾干/祖细胞具有分化成JG样细胞的能力 细胞和/或有助于 JG 细胞扩增。在第二个项目中，他参与了一项研究，发现肾脏 MSC 通过 Cox2-PGE2-EP4 途径招募。他还研究了成人的机制 干细胞分化成专门的组织，并确定 Sfrp2 在心脏中发挥重要作用 通过促进 c-Kit+ 心脏祖细胞分化为心肌细胞来实现再生。现在作为一个 范德比尔特大学临床讲师，在 David Harrison 博士的指导下，他正在阐明 在肾祖细胞编程为肾小球旁细胞中发挥作用的转录调节因子 细胞。他发现 Sox6 在发育中的肾脏和成年肾脏的肾素产生细胞中表达 刺激后促进 JG 细胞扩增。这表明 Sox6 在肾素细胞命运中的新作用 规范，从而影响肾脏发育和生理学。他的初步数据表明 Sox6 是 肾间充质干细胞在体外转化为肾素表达细胞所需的。在这个K01提案中，他将 表征了 Sox6 在血压稳态和肾小球旁细胞命运中的新关键功能。这 本 K01 中提出的研究旨在确定 Sox6 在血压中发挥作用的机制 体内平衡，将为高血压的治疗开辟新的机遇。 在他计划的研究期间，戈麦斯博士将在体外和体内研究方法方面积累经验 高血压。此外，他的培训计划包括教学课程、研讨会和参与职业生涯 范德比尔特大学的发展计划旨在促进初级教员的保留和终身任职。博士。 哈里森和戈麦斯博士为他的职业发展和培训活动制定了时间表，这将 使他能够竞争资金并发展成为高血压领域的独立研究者。 他 100% 的时间将被保护用于与他的职业发展直接相关的活动。范德比尔特 大学的研究和学术环境对于学员的职业发展来说非常优越。

项目成果

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis.

肾动脉狭窄中肾素调节的改良两肾一夹小鼠模型。

• DOI: 10.3791/61058
• 发表时间: 2020
• 期刊: Journal of visualized experiments : JoVE
• 作者: Saleem,Mohammad;Barturen-Larrea,Pierina;Saavedra,Luz;Gomez,JoseA
• 通讯作者: Gomez,JoseA

The role of Sfrp and DKK proteins in cardiomyocyte development.

• DOI: 10.14814/phy2.14678
• 发表时间: 2021-03
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Hsueh YC;Hodgkinson CP;Gomez JA
• 通讯作者: Gomez JA

Emerging roles of Sox6 in the renal and cardiovascular system.

• DOI: 10.14814/phy2.14604
• 发表时间: 2020-11
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Saleem M;Barturen-Larrea P;Gomez JA
• 通讯作者: Gomez JA

The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis.

转录因子 Sox6 在肾动脉狭窄期间控制肾素表达。

• DOI: 10.34067/kid.0002792020
• 发表时间: 2021
• 期刊: Kidney360
• 作者: Saleem,Mohammad;Saavedra-Sánchez,Luz;Barturen-Larrea,Pierina;Gomez,JoseA
• 通讯作者: Gomez,JoseA