Fucoidan elevates surface organic cation transporter 2 expression via upregulation of protein kinase A in uric acid nephropathy

Wu,Xinlin; Yan,Miansheng; Liu,Taoli; Liao,Jiantang; Zhang,Jianqing; Chen,Shuqing; Deng,Wei; Zhang,Shijun; Sun,Baoguo; Zhou,Houming; Ke,Bin

doi:10.3892/etm.2017.5077

Fucoidan elevates surface organic cation transporter 2 expression via upregulation of protein kinase A in uric acid nephropathy

Authors:
- Xinlin Wu
- Miansheng Yan
- Taoli Liu
- Jiantang Liao
- Jianqing Zhang
- Shuqing Chen
- Wei Deng
- Shijun Zhang
- Baoguo Sun
- Houming Zhou
- Bin Ke
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Affiliations: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Sun Yat‑sen University, Zhuhai, Guangdong 519000, P.R. China, Community Health Service Center of Dongshan, Guangzhou, Guangdong 510030, P.R. China
Published online on: August 30, 2017 https://doi.org/10.3892/etm.2017.5077
Pages: 4153-4159
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uric acid nephropathy (UAN) is caused by excessive uric acid, and is a key risk factor for uric acid nephrolithiasis, gouty arthritis, renal diseases and cardiovascular diseases. The present study aimed to evaluate the protective effect of fucoidan, a sulfated polysaccharide component of brown algae, on UAN and to elucidate the underlying molecular mechanism. A rat model of UAN was induced by adenine treatment, and rats were then randomly assigned to control, model or fucoidan treatment groups. Hematoxylin and eosin staining of the kidney tissues of rats with UAN was subjected to conventional morphological evaluation. Cellular infiltrate in the tubules, atrophic glomeruli, tubular ectasia, granuloma hyperplasia focal fibrosis and accumulated urate crystals in the tubules of UAN rat renal tissues were observed. These symptoms of kidney damage were reduced in the fucoidan treatment group. Periodic acid methenamine silver‑Masson staining was performed and the results indicated that renal interstitial fibrosis was reduced among renal tissues from the fucoidan treatment group compared with the model group. Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling staining revealed a lower proportion of apoptotic nuclei in the kidneys of the fucoidan treatment group compared with the model group. Protein kinase A (PKA) 2β and phosphorylated PKA 2β protein levels were significantly elevated in renal tissues of the fucoidan treatment group compared with the model group (P<0.05 and P<0.01, respectively), suggesting that PKA expression was upregulated by fucoidan. Immunohistochemistry staining of PKA in rat renal tissues demonstrated increased expression of PKA. The surface organic cation transporter 2 (OCT2) level was significantly increased by fucoidan treatment compared with the model group (P<0.01), with no significant change in total OCT2 level. COS‑7 cells ectopically expressing OCT2 were established. It was indicated that fucoidan was able to activate PKA and upregulate surface OCT2 in OCT2‑expressing COS‑7 cells. This further demonstrated that upregulation of surface OCT2 expression in OCT2‑expressing cells was induced by PKA upregulation. In conclusion, fucoidan upregulated surface OCT2 expression in renal tissues to alleviate the symptoms of UAN via upregulated expression of PKA.

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