Mechanisms and therapeutic manipulation of retinoic acid signaling in Acute Kidney Injury
急性肾损伤中视黄酸信号传导的机制和治疗操作
基本信息
- 批准号:9924588
- 负责人:
- 金额:$ 42.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAcute Renal Failure with Renal Papillary NecrosisAgonistAnimal ModelAristolochic AcidsBiological ModelsC10Cell Culture TechniquesCellsChronic Kidney FailureClinical TreatmentDNA BindingDevelopmentDiseaseDoseEnd stage renal failureEpithelial CellsFibrosisGenetic TranscriptionHealthcareHourHumanIn VitroInflammationInflammatoryInjuryInjury to KidneyIschemiaKidneyKidney DiseasesMediatingMetabolismModelingMusObstructionPathway interactionsPatientsPharmaceutical PreparationsPhasePlayPre-Clinical ModelProcessProteinsRecoveryRecovery of FunctionRenal functionReperfusion TherapyReportingRepressionResolutionRetinoic Acid ReceptorRetinoidsRisk FactorsRoleSeriesSeveritiesSignal PathwaySignal TransductionSiteTestingTherapeuticTretinoinTubular formationWorkbasechemokinehuman diseaseimprovedin vitro Modelin vivoinjury and repairkidney fibrosismacrophagemortalitynephrogenesisnovelnovel therapeuticspre-clinicalpreservationrecruitrepairedresponseresponse to injurysystemic toxicitytherapeutic targettissue injurytissue regenerationtissue repairtreatment response
项目摘要
Acute kidney injury (AKI) is a serious disorder that involves a rapid decline in renal function over a period of hours to
days. Severe cases can result in end-stage renal disease, and evidence suggests that AKI is a precursor to long-term
chronic renal disease (CKD). Despite this, there is no targeted clinical treatment for AKI. Specifically, no therapies exist
that accelerate renal recovery or decrease fibrosis and CKD when administered after injury. However, the kidney
possesses an inherent capacity to repair after AKI, and a promising approach to ameliorate long-term AKI-mediated
damage lies in developing novel therapies that can enhance the natural mechanisms of tissue repair in order to reduce
fibrosis and CKD after AKI. Macrophages play a central role in coordinating the injury and repair process after AKI, but
the intrinsic mechanisms control macrophage-dependent repair after AKI have been poorly understood. In recent studies
we have shown that retinoic acid (RA) signaling plays an important role in regulating this macrophage-dependent repair
and fibrosis after AKI and that therapeutic manipulation of this pathway might be used to safely manipulate this RA-
dependent response for therapeutic benefit for AKI. In this proposal we plan a series of mouse and cell culture studies to
explore the mechanisms by which RA signaling regulates this response, and to develop a novel pre-clinical therapeutic
platform to safely and effectively enhance local activation of the RA signaling pathway in the kidney in order to increase
macrophage-dependent tissue repair and reduce the likelihood of developing long-term CKD after an episode of AKI.
急性肾损伤(AKI)是一种严重的疾病,涉及肾功能在一段时间内迅速下降
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transdermal Measurement of Glomerular Filtration Rate in Mice.
- DOI:10.3791/58520
- 发表时间:2018-10-21
- 期刊:
- 影响因子:0
- 作者:Scarfe L;Schock-Kusch D;Ressel L;Friedemann J;Shulhevich Y;Murray P;Wilm B;de Caestecker M
- 通讯作者:de Caestecker M
Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.
缺血再灌注诱导的急性肾损伤小鼠模型的长期结果。
- DOI:10.1152/ajprenal.00305.2019
- 发表时间:2019
- 期刊:
- 影响因子:0
- 作者:Scarfe,Lauren;Menshikh,Anna;Newton,Emily;Zhu,Yuantee;Delgado,Rachel;Finney,Charlene;deCaestecker,MarkP
- 通讯作者:deCaestecker,MarkP
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mark P. de Caestecker其他文献
Serine Phosphorylation, Chromosomal Localization, and Transforming Growth Factor-β Signal Transduction by Human <strong><em>bsp-1</em></strong>
- DOI:
10.1074/jbc.271.30.17617 - 发表时间:
1996-07-26 - 期刊:
- 影响因子:
- 作者:
Robert J. Lechleider;Mark P. de Caestecker;Anindya Dehejia;Mihael H. Polymeropoulos;Anita B. Roberts - 通讯作者:
Anita B. Roberts
Experimental models of acute kidney injury for translational research
用于转化研究的急性肾损伤实验模型
- DOI:
10.1038/s41581-022-00539-2 - 发表时间:
2022-02-16 - 期刊:
- 影响因子:39.800
- 作者:
Neil A. Hukriede;Danielle E. Soranno;Veronika Sander;Tayla Perreau;Michelle C. Starr;Peter S. T. Yuen;Leah J. Siskind;Michael P. Hutchens;Alan J. Davidson;David M. Burmeister;Sarah Faubel;Mark P. de Caestecker - 通讯作者:
Mark P. de Caestecker
Functional significance of CITED1 overexpression and nuclear localization in Wilms tumor
- DOI:
10.1016/j.jamcollsurg.2012.06.216 - 发表时间:
2012-09-01 - 期刊:
- 影响因子:
- 作者:
Andrew Jackson Murphy;Janene Pierce;Christian de Caestecker;Alan O. Perantoni;Mark P. de Caestecker;Harold N. Lovvorn - 通讯作者:
Harold N. Lovvorn
Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy.
人 IgA 肾病外周血单核细胞细胞因子网络异常的检测。
- DOI:
- 发表时间:
1993 - 期刊:
- 影响因子:19.6
- 作者:
Mark P. de Caestecker;Martin Bottomley;Brian A. Telfer;Ian V. Hutchinson;Brent M. Vose;Francis W. Ballardie - 通讯作者:
Francis W. Ballardie
Mark P. de Caestecker的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mark P. de Caestecker', 18)}}的其他基金
FASEB SRC on Acute Kidney Injury: from beside to bench (and back again)
FASEB SRC 关于急性肾损伤:从旁边到替补(然后再回来)
- 批准号:
9752908 - 财政年份:2019
- 资助金额:
$ 42.67万 - 项目类别:
Vanderbilt Kidney O'brien Center - Enrichment Program
范德比尔特肾脏奥布莱恩中心 - 浓缩计划
- 批准号:
10163171 - 财政年份:2017
- 资助金额:
$ 42.67万 - 项目类别:
Mechanisms and therapeutic manipulation of retinoic acid signaling in Acute Kidney Injury
急性肾损伤中视黄酸信号传导的机制和治疗操作
- 批准号:
9332756 - 财政年份:2017
- 资助金额:
$ 42.67万 - 项目类别:
Mutation Specific Therapies in Patients with HPAH
HPAH 患者的突变特异性治疗
- 批准号:
8518456 - 财政年份:2012
- 资助金额:
$ 42.67万 - 项目类别:
Mutation Specific Therapies in Patients with HPAH
HPAH 患者的突变特异性治疗
- 批准号:
8356472 - 财政年份:2012
- 资助金额:
$ 42.67万 - 项目类别:
A mouse model of placental insufficiency with abnormal renal medullary patterning
胎盘功能不全伴肾髓质模式异常的小鼠模型
- 批准号:
7585522 - 财政年份:2009
- 资助金额:
$ 42.67万 - 项目类别: