title: Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy.
abstract: 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.
  
  
  METHODS
  Most relevant articles were mainly identified by searching PubMed in English.
  
  
  METHODS
  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 pro-inflammatory cytokines, which leads to fibronectin, transforming growth factor-β1 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.
authors.affiliation: Department of Pharmacy, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Vascular Biology, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Email: huangheq@mail.sysu.edu.cn.
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
mesh_terms: D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate