Fucoidan Attenuated Kidney and Bone Damage Caused by CKD-MBD in Mice by Upregulating Klotho

Abstract

Background Fucoidan is a phosphorylated polysaccharide extracted from seaweed that has a renal protective effect. However, whether Fucoidan can be used to prevent chronic kidney disease with mineral and bone disorders (CKD-MBD) is still a mystery and thus becomes the target of this research. Materials and Methods CKD-MBD mouse models were constructed, and the effects of Fucoidan and Klotho on CKD-MBD were determined through treatment of Fucoidan (100 mg/kg or 200 mg/kg) by gavage or tail vein injection of Klotho specific to small interfering RNA (siKlotho). The biochemical indicators related to renal function and bone metabolism in serum were detected by an automatic biochemical analyzer or enzyme-linked immunosorbent assay. Bone density was measured by X-ray. The effect of Fucoidan or siKlotho on kidney damage was tested by hematoxylin and eosin (H&E) staining or Elastica Masson-Goldner (EMG) staining. The expressions of Klotho, Runt-related transcription factor 2 (Runx2), and α-smooth muscle actin (α-SMA) in kidney tissue after Fucoidan treatment and/or siKlotho injection were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, or Western blot. Results Fucoidan treatment inhibited the levels of blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), phosphorus, intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF23), while promoting 1,25 (OH)2D3 levels in serum. Fucoidan also increased bone density in mice, alleviated kidney damage and fibrosis of kidney tissue, promoted the expression of Klotho and Runx2, and inhibited the expression of α-SMA in kidney tissue. However, the above-mentioned therapeutic effects of Fucoidan were all reversed by siKlotho. Conclusion Fucoidan prevents CKD-MBD by up-regulating Klotho levels.