Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF‑β1/Smad/miR‑192 signaling pathway

Mao,Qian; Chen,Cuicui; Liang,Huankun; Zhong,Shuhai; Cheng,Xinbo; Li,Laiqing

doi:10.3892/etm.2019.7887

Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF‑β1/Smad/miR‑192 signaling pathway

Authors:
- Qian Mao
- Cuicui Chen
- Huankun Liang
- Shuhai Zhong
- Xinbo Cheng
- Laiqing Li
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Affiliations: Department Endocrinology, Hospital of Beihua University, Jilin, Jilin 132013, P.R. China, Guangzhou Youdi Bio‑Technology Co., Ltd., Guangzhou, Guangdong 510663, P.R. China, Department of Endocrinology and Metabolism, Hospital of Soochow University, Suzhou, Jiangsu 210506, P.R. China
Published online on: August 14, 2019 https://doi.org/10.3892/etm.2019.7887
Pages: 3053-3061
Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Astragaloside IV (ASI) exhibits a wide variety of pharmacological effects in cardiovascular diseases, hepatitis and kidney disease and due to this, ASI has recently become an attractive research target. The present study aimed to determine the effect of ASI on renal fibrosis and the mechanisms underlying its therapeutic effects in diabetic nephropathy (DN). In vitro, ASI was added to rat mesangial cells (RMCs) and cultured with a high level of glucose (HG) to observe the effects exhibited on proliferation and fibrosis‑related mRNA and protein expression. In vivo, a DN model was established using streptozotocin administration in rats, and renal injury was evaluated using renal histological examination. The expression levels of related mRNAs and proteins were analyzed using reverse transcription‑quantitative PCR, western blot analysis and immunohistochemistry. ASI was demonstrated to downregulate miR‑192 expression and inhibit excessive proliferation of RMCs, which was induced by HG, in a dose‑dependent manner. Additionally, ASI exhibited a therapeutic effect on DN rats. ASI was also demonstrated to decrease the miR‑192 expression and mRNA and protein expression of transforming growth factor‑β1 (TGF‑β1), Smad3, α‑smooth muscle actin (α‑SMA) and collagen type 1 (col1), and increase the mRNA and protein expression of Smad7 in vitro and in vivo. These results suggested that ASI exhibited a therapeutic effect on DN, possibly due to the inhibition of excessive mesangial proliferation and renal fibrosis via the TGF‑β1/Smad/miR‑192 signaling pathway.

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