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Metabolomics study on the preventive mechanisms for LDR on diabetic nephropathy

LDR预防糖尿病肾病机制的代谢组学研究

基本信息

批准号：
8806238
负责人：
Lu Cai
金额：
$ 15万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8806238
关键词：
Adverse effects Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Apoptotic Biological Cell Death Cell Nucleus Cell Proliferation Complications of Diabetes Mellitus Cytogenetics Cytosol Data Diabetes Mellitus Diabetic Nephropathy Diabetic mouse Disease Dose Drug Combinations Drug Targeting Drug usage Frequencies Genes Germ Cells Glycogen Synthase Kinase 3 Goals Harvest In Vitro Inflammation Kidney Kidney Diseases Kidney Failure Low Dose Radiation Mediating Methods Modality Modeling Mus Organ Pathway interactions Pharmaceutical Preparations Phosphorylation Prevention Preventive Protein Tyrosine Kinase Proto-Oncogene Proteins c-akt Proto-Oncogenes Radiation Radiation therapy Reactive Oxygen Species Renal function Renin-Angiotensin System Risk Rodent Role Safety Streptozocin Testing Therapeutic Therapeutic Effect Tissues Toxic effect Up-Regulation Work cytotoxic diabetic diabetic patient in vivo innovation metabolomics mouse model novel strategies novel therapeutic intervention nuclear factor-erythroid 2 oxidative damage prevent public health relevance repaired response safety testing tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): The goal of this study is to develop low-dose radiation (LDR) as a new tool to prevent and treat diabetic nephropathy. Currently no effective preventive or therapeutic approaches are available to treat diabetic nephropathy, which is the most common cause of renal failure. We have been investigating the biological effects of LDR, including its hormesis and adaptive response, in vitro and in vivo. A major advantage of LDR is that it activates many genes in antioxidant and anti-inflammatory pathways, rather than just single protective gene, potentially making LDR a very potent and novel therapeutic approach. This was borne out by our preliminary studies that show that LDR at 25 mGy decreases diabetic nephropathy, by significantly reducing diabetes-induced renal oxidative damage and inflammation. Our latest preliminary data show up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression and protein kinase B (also called Akt) phosphorylation in the kidney of diabetic mice, also exposed to LDR at 25 mGy. NRF2 is a transcription factor involved in expression of a broad range of protective genes. Therefore our central hypothesis is that exposure of diabetic animals to LDR can prevent and treat diabetic nephropathy by activation of many protective genes through stimulation of the Nrf2 pathway. This hypothesis will be tested through three specific Aims: (1) LDR at the optimal condition not only prevents, but also delay diabetic nephropathy; (2) the optimal LDR is safe for diabetic subjects; (3) the renal protection by the optimal LDR is predominantly mediated by up- regulating Nrf2-mediated multiple antioxidant components. The great advantage of LDR is that it offers a highly controllable, non-invasive method for eliciting endogenous, synergistic tissue protection and repair mechanisms. This innovative approach will be particularly valuable for the diabetic patient who already has significantly decreased renal function that increases the toxicity of invasive drugs. Therefore, this project will open a new avenue for the prevention and treatment of diabetic complications.

描述（由申请人提供）：

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation.

糖尿病微血管疾病和肺纤维化：血小板和全身炎症的贡献。

DOI：
10.3390/ijms17111853
发表时间：
2016-11-08
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Jagadapillai R;Rane MJ;Lin X;Roberts AM;Hoyle GW;Cai L;Gozal E
通讯作者：
Gozal E

C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21.

C66通过增加miR-200a和抑制miR-21的上调NRF2功能来改善小鼠中的糖尿病性肾病。

DOI：
10.1007/s00125-016-3958-8
发表时间：
2016-07
期刊：
Diabetologia
影响因子：
8.2
作者：
Wu H;Kong L;Tan Y;Epstein PN;Zeng J;Gu J;Liang G;Kong M;Chen X;Miao L;Cai L
通讯作者：
Cai L

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation.

DOI：
10.1016/j.bbadis.2014.11.006
发表时间：
2015-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
影响因子：
6.2
作者：
Wang, Yangwei;Wang, Yonggang;Luo, Manyu;Wu, Hao;Kong, Lili;Xin, Ying;Cui, Wenpeng;Zhao, Yunjie;Wang, Jingying;Liang, Guang;Miao, Lining;Cai, Lu
通讯作者：
Cai, Lu

Alterations of MicroRNA Expression in the Liver, Heart, and Testis of Mice Upon Exposure to Repeated Low-Dose Radiation.