Effects of tanshinone IIA on the regulation of renal proximal tubular fibrosis

Cao,Luoyuan; Huang,Baoying; Fu,Xianguo; Yang,Jing; Lin,Yinghua; Lin,Feng

doi:10.3892/mmr.2017.6498

Effects of tanshinone IIA on the regulation of renal proximal tubular fibrosis

Authors:
- Luoyuan Cao
- Baoying Huang
- Xianguo Fu
- Jing Yang
- Yinghua Lin
- Feng Lin
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Affiliations: Department of Central Laboratory, Ningde Municipal Hospital, Affiliated Hospital of Fujian Medical University, Ningde, Fujian 352100, P.R. China
Published online on: April 21, 2017 https://doi.org/10.3892/mmr.2017.6498
Pages: 4247-4252

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Abstract

The development of diabetes mellitus, along with its complications, is a chronic inflammatory response process. Chronic kidney diseases are characterized by renal ﬁbrosis, and fibrosis is an important pathway for end‑stage renal failure. According to previous studies, high glucose (HG) has been demonstrated to be the most important fibrogenesis‑inducing agent. Tanshinone IIA is one of the main components isolated from Danshen (Salvia miltiorrhiza). Although tanshinone IIA has been widely used for the treatment of cardiovascular diseases, the possible role of tanshinone IIA in fibrosis regulation remains to be elucidated and requires investigation. In the present study, renal proximal tubular epithelial cells (HK‑2) were treated with HG (30 mM glucose) to determine whether tanshinone IIA (1, 10 and 50 µM) had an effect on the regulation of renal cellular fibrosis. The results demonstrated that 50 µM tanshinone IIA may exert optimal inhibitory effects on HG‑induced Snail, fibronectin, vimentin and α‑smooth muscle actin (α‑SMA) expression in HK‑2 cells after 48 h. Tanshinone IIA also reversed HG‑induced morphological alterations in HK‑2 cells and inhibited an HG‑induced increase in fibronectin and α‑SMA mRNA and protein and an HG‑induced decrease in E‑cadherin. Furthermore, tanshinone IIA suppressed an HG‑induced increase in Snail, which is a transcription factor that can suppress E‑cadherin expression. E‑cadherin is a major component of adherens junctions and a characteristic of epithelial integrity. Tanshinone IIA reversed HG‑induced increase in α‑SMA and decrease in E‑cadherin. These data suggest that tanshinone IIA has the potential to inhibit HG‑induced renal tubular epithelial cell fibrosis possibly through the epithelial‑myofibroblast transdifferentiation pathway. Therefore, tanshinone IIA may be considered a renoprotective agent for the treatment of renal fibrosis.

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