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.