Oligo-Fucoidan Improves Diabetes-Induced Renal Fibrosis via Activation of Sirt-1, GLP-1R, and Nrf2/HO-1: An In Vitro and In Vivo Study.

Abstract

Fucoidan extracted from brown algae has multiple beneficial functions. In this study, we investigated the effects of low-molecular-weight fucoidan (oligo-FO) on renal fibrosis under in vitro and in vivo diabetic conditions, and its molecular mechanisms. Advanced glycation product (AGE)-stimulated rat renal proximal tubular epithelial cells (NRK-52E) and diabetic mice induced by high-fat diet and intraperitoneal injection of streptozotocin and nicotinamide were used. Oligo-FO treatment significantly inhibited anti-high mobility group box 1 (HMGB1)/RAGE/ anti-nuclear factor-kappa B (NF-κB)/transforming growth factor-β1 (TGF-β1)/TGF-β1R/Smad 2/3/fibronectin signaling pathway and HIF-1α activation in AGE-stimulated NRK-52E cells. Conversely, the expression and activity of Sirt-1; the levels of ubiquitin-specific peptidase 22 (USP22), p-AMPK, glucagon-like peptide-1 receptor (GLP-1R), and heme oxygenase-1 (HO-1); and Nrf2 activation were remarkably increased by oligo-FO in AGE-stimulated cells. However, the above effects of oligo-FO were greatly diminished by inhibiting Sirt-1, HO-1, or GLP-1R activity. Similar changes of these pro-fibrotic genes in the kidney and a marked attenuation of renal injury and dysfunction were observed in oligo-FO-treated diabetic mice. These findings indicated that the inhibitory effects of the oligo-FO on diabetes-evoked renal fibrosis are mediated by suppressing TGF-β1-activated pro-fibrogenic processes via Sirt-1, HO-1, and GLP-1R dependence. Collectively, fucoidan-containing foods or supplements may be potential agents for ameliorating renal diseases due to excessive fibrosis.

• Authors: Wen-Chun Yu, Ren-Yeong Huang, Tz-Chong Chou
• Journal: Nutrients (Nutrients) Vol. 12 Issue 10 (Oct 08 2020) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 33049944 (Publication Type: Journal Article)

Chemical References

• Glp1r protein, mouse
• Glucagon-Like Peptide-1 Receptor
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Polysaccharides
• fucoidan
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Cells, Cultured
• Diabetic Nephropathies (drug therapy, genetics)
• Dietary Supplements
• Fibrosis (drug therapy, genetics)
• Gene Expression (drug effects)
• Glucagon-Like Peptide-1 Receptor (genetics, metabolism)
• Heme Oxygenase-1 (genetics, metabolism)
• Kidney (pathology)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice, Inbred C57BL
• Molecular Weight
• NF-E2-Related Factor 2 (genetics, metabolism)
• Nutritional Physiological Phenomena (physiology)
• Phaeophyceae (chemistry)
• Phytotherapy
• Polysaccharides (administration & dosage, chemistry, isolation & purification, pharmacology)
• Rats
• Sirtuin 1 (genetics, metabolism)