Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy  

作　　者：Deng Yanhui Lan Tian Huang Juan Huang Heqing 

机构地区：[1]Department of Pharmacy, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China [2]Institute of Vascular Biology, Guangdong Pharmaceutical University,Guangzhou, Guangdong 510006, China [3]Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou,Guangdong 510006, China

出　　处：《Chinese Medical Journal》2014年第16期3004-3010,共7页中华医学杂志（英文版）

基　　金：This work was supported by research grants from the Natural Science Foundation of China （No. 81170676, 81373457） and Natural Science Foundation of Guangdong Province （No.S2012020010991, S2013010015765）.

摘　　要：Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.

关 键 词：diabetic nephropathy sphingosine kinase-1 sphingosine 1-phosphate FIBROSIS transforming growth factor-β extracellular matrix 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]