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Low molecular weight fucoidan against diabetic nephropathy (1051.17)
Author(s) -
Zhou Hong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1051.17
Subject(s) - ctgf , endocrinology , medicine , diabetic nephropathy , protein kinase b , fibronectin , kidney , smad , mapk/erk pathway , chemistry , transforming growth factor , growth factor , signal transduction , cell , biochemistry , receptor
The objective of the present study was to investigate the therapeutic effect and underlying mechanisms of LMWF on diabetic nephropathy.LMWF was administered to the diabetic rats at a daily dose of 100 mg/kg body weight by intragastric administration. Following 12 weeks treatment, we measured body and kidney weight, blood glucose, blood pressure, creatinine and urea concentration in serum and urine, urine output, urinary osmolality, urinary protein excretion. α‐SMA, E‐cadherin, fibronectin, TGF‐β1, CTGF were measured by Western blot to evaluate the level of epithelial‐to‐mesenchymal transition (EMT). In addition, the phosphorylation of Akt, Smad3, p38 and ERK in renal tissue were evaluated. In virio , HK2 renal tubular epithelial cells pretreated with LMWF were stimulated by the recombinant human TGF‐β1 (10 ng/ml) for 48 h. α‐SMA, vimentin, E‐cadherin, fibronectin, CTGF were measured by Western blot to evaluate the level of EMT. In addition, activity of Akt, Smad and MAPK signal pathway in HK2 cell were evaluated.Renal expression of TGF‐β1, CTGF, fibronectin and α‐SMA protein were increased significantly in diabetic rats compared to those in the controls. E‐cadherin protein expression in diabetic kidneys decreased significantly. LMWF effectively reduced hypertension, proteinuria, renal TGF‐β1, CTGF, fibronectin and α‐SMA up‐regulation, as well as renal E‐cadherin down‐regulation in diabetic rats without a significant effect on blood glucose. LMWF also inhibited the activation of Smad, Akt, MAPK pathways. In vitro , LMWF alleviated TGF‐β1 induced EMT in HK2 cells via inhibition of Smad, Akt, MAPK pathways in a dose‐dependent manner. Our in vivo and in vitro studies show that LMWF ameliorates diabetic nephropathy, possibly through inhibiting the expression of TGF‐β1 and Smad, Akt, MAPK signaling pathways downstream, then subsequent suppressing EMT. The data provide evidence that LMWF may serve as a potential therapeutic agent for diabetic nephropathy.