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[11-14]Metabolic Profiling Reveals Soluble Epoxide Hydrolase as a Therapeutic Target for Obesity-mediated Kidney Injury

发布者:彭蓓发布时间:2019-11-08浏览次数:10

报告题目:Metabolic Profiling Reveals Soluble Epoxide Hydrolase as a Therapeutic Target forObesity-mediated Kidney Injury

报 告 人:刘俊彦 博士(同济大学附属上海第十人民医院)

报告时间:20191114日(星期四)上午9:00

报告地点:药学院云轩楼2301会议室


报告人简介:

Dr. Jun-Yan Liu is currently a Professor of Shanghai Tenth People’s Hospital of Tongji University, and Deputy Director of the Center for Nephrology and Metabolomics, Tongji University School of Medicine. Dr. Liu was conferred his Ph.D. degree by Nanjing University in 2003. He then received postdoctoral training at Nanjing University (2003/06-2005/04) and University of California Davis (UCD) (2005/05-2009/05). He was appointed as an Assistant Research Scientist of UCD during 2009/06-2012/10 and the Co-Core Leader of the Analytical Core of NIEHS-UCD Superfund Basic Research Program (2011/03-2012/09). During 2012/10-2014/04, Dr. Liu worked as a Senior Research Scientist for Marrone Bio Innovations (CA, USA). In 2014/05, Dr. Liu joined Shanghai Tenth People’s Hospital of Tongji University. Dr. Liu’s research interest includes Bioanalytical Chemistry/Metabolomics, Pharmacokinetics/Pharmacology, and Natural Medicinal Chemistry. He has over 60 papers published in internationally peer-reviewed journals, such as PNAS, Cancer Research, Molecular Cancer Therapeutics,British Journal of Pharmacology, Biochemical Pharmacology, etc. He serves as the peer reviewer of NSFC, Ministry of Education of China Science and Technology Evaluation and Review system, and Shanghai Science and Technology Committee (STCSM), as well as over 10 international peered reviewed journals such as Cancer Immunology Research, Trends in Analytical Chemistry, Biochemical Pharmacology, Oxidative Medicine and Cellular Longevity, etc.

报告摘要:

Obesity-mediated kidney injury (OMKI) has become a global public health concern for the ascending prevalence of obesity. However, the pathologic and pharmacologic mechanisms of OMKI remain largely unknown. Here we showed that soluble epoxide hydrolase (sEH) is a novel therapeutic target for OMKI in a murine model of high-fat diet (HFD)-caused obesity by using a LC-MS/MS-based metabolomics method. Specifically, mice fed on a HFD for 2, 4, and 8 weeks showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, as well as the significant increase in renal sEH at mRNA, protein, and molecular levels. Administration of a sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused a significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. 14(15)-EET (a major substrate of sEH) but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1 and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides novel insights into and a therapeutic target for HFD-mediated renal injury.