Low molecular weight fucoidan ameliorates diabetic nephropathy via inhibiting epithelial-mesenchymal transition and fibrotic processes

• Published in: American journal of translational research Vol. 7; no. 9; pp. 1553 - 1563
• Main Authors: Chen, Jihui, Cui, Wentong, Zhang, Quanbin, Jia, Yingli, Sun, Yi, Weng, Lin, Luo, Dali, Zhou, Hong, Yang, Baoxue
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01-01-2015
• Subjects: Original; transforming growth factor-β1; epithelialto-mesenchymal transition; tubulointerstitial fibrosis; Fucoidan; diabetic nephropathy; extracellular matrix
• ISSN: 1943-8141; 1943-8141

Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and may lead to end-stage renal disease (ESRD) and chronic renal failure. The aim of this study was to determine whether low-molecular-weight fucoidan (LMWF) can reduce harmful transforming growth factor-β (TGF-β)-mediated renal fibrosis in DN using in vitro and in vivo experimental models. The experimental results showed that LMWF significantly reversed TGF-β1-induced epithelial-mesenchymal transition and dose-dependently inhibited accumulation of extracellular matrix proteins, including connective tissue growth factor and fibronectin. It was found that LMWF significantly reduced blood urea nitrogen and blood creatinine in both type 1 and type 2 diabetic rat models. H&E, PAS and Masson's trichrome staining of kidney tissue showed LMWF significantly reduced renal interstitial fibrosis. Treatment with LMWF significantly increased E-cadherin expression and reduced α-SMA, CTGF and fibronectin expression in both type 1 and type 2 diabetic models. LMWF also decreased the phosphorylation of Akt, ERK1/2, p38 and Smad3 in vitro and in vivo. These data suggest that LMWF may protect kidney from dysfunction and fibrogenesis by inhibiting TGF-β pathway and have the potential benefit to slow down the progression of DN.