title: Low molecular weight fucoidan ameliorates diabetic nephropathy via inhibiting epithelial-mesenchymal transition and fibrotic processes.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China ; Department of Pharmacy, Xin-Hua Hospital Affiliated to Medical School, Shanghai Jiao Tong University Shanghai 200092, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Capital Medical University Beijing 100069, China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Cui
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences Qingdao 266071, China.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Pharmacology, Capital Medical University Beijing 100069, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University Beijing 100191, China.
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
keywords: Fucoidan; diabetic nephropathy; epithelialto-mesenchymal transition; extracellular matrix; transforming growth factor-β1; tubulointerstitial fibrosis