American Journal of Translational Research | |
Low molecular weight fucoidan ameliorates diabetic nephropathy via inhibiting epithelial-mesenchymal transition and fibrotic processes | |
Jihui Chen1  | |
关键词: Fucoidan; diabetic nephropathy; epithelialto-mesenchymal transition; transforming growth factor-β; 1; extracellular matrix; tubulointerstitial fibrosis; | |
DOI : | |
学科分类:医学(综合) | |
来源: e-Century Publishing Corporation | |
【 摘 要 】
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.
【 授权许可】
CC BY-NC
【 预 览 】
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RO201904033639324ZK.pdf | 1811KB | download |