Sulodexide improves renal function through reduction of vascular endothelial growth factor in type 2 diabetic rats

Jin Joo Cha, Young Sun Kang, Young Youl Hyun, Sang Youb Han, Yi Hwa Jee, Kum Hyun Han, Jee Young Han, Dae Ryong Cha

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Aims Sulodexide is a promising therapeutic drug for the management of diabetic nephropathy. Although sulodexide has demonstrated a renoprotective effect through its ability to restore glomerular ionic permselectivity, the exact mechanism is still not clear. We investigated the effects of long-term sulodexide treatment on diabetic nephropathy in Otsuka-Long-Evans-Tokushima- Fatty (OLETF) rats. Main methods Diabetic rats were treated with or without sulodexide at 10 mg/kg/day in the drinking water for nine months. Renal morphology and changes in VEGF and p38 mitogen-activated protein kinase (p38 MAPK), urinary levels of albumin (UAE) and urinary VEGF excretion were determined. To define the direct effects of sulodexide, we performed an in vitro experiment using podocytes. Key findings UAE was significantly higher in OLETF rats than in control LETO rats, and the sulodexide group showed significantly decreased UAE after six months of treatment. Interestingly, urinary VEGF levels were also significantly decreased in the sulodexide-treated group. In accordance with UAE and urinary VEGF changes, the renal expression of profibrotic molecules was significantly decreased after sulodexide treatment. In addition, the activation of p38 MAPK, assessed by measuring the level of phospho-specific p38 MAPK, increased in diabetic renal tissues and was markedly suppressed by sulodexide treatment. In cultured podocytes, sulodexide treatment significantly decreased high glucose-induced p38 MAPK activation and VEGF synthesis. Significance Sulodexide directly suppresses VEGF synthesis through the p38 MAPK pathway in podocytes, and these results suggest that sulodexide may provide renoprotection via suppression of renal VEGF synthesis independently of glomerular basement membrane ionic permselectivity in type 2 diabetic rats.

Original languageEnglish
Pages (from-to)1118-1124
Number of pages7
JournalLife Sciences
Issue number23
Publication statusPublished - 2013 Jun 21
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd. for providing the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We also thank the Alfa Wassermann, Italy for kindly providing sulodexide. This work was supported by a Korea Research Foundation grant ( R1008581 ).


  • Diabetic nephropathy
  • Type 2 diabetes mellitus
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry,Genetics and Molecular Biology


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