Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Tanshinone IIA mitigates peritoneal fibrosis by inhibiting EMT via regulation of TGF-β/smad pathway

Qiuyuan Shao, Chunming Jiang, Cheng Sun, Wei Zhu, Dongwei Cao, Yuan Feng, Miao Zhang

Department of Nephrology, Drum Tower Hospital Affiliated to School of Medicine, Nanjing University, Nanjing, China;

For correspondence:- Miao Zhang Email: zhmiao19@126.com

Accepted: 30 November 2017 Published: 29 December 2017

Citation: Shao Q, Jiang C, Sun C, Zhu W, Cao D, Feng Y, et al. Tanshinone IIA mitigates peritoneal fibrosis by inhibiting EMT via regulation of TGF-β/smad pathway. Trop J Pharm Res 2017; 16(12):2857-2864 doi: 10.4314/tjpr.v16i12.9

© 2017 The authors.
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Abstract

Purpose: To explore the effects of tanshinone IIA (T-IIA) on Dianeal-N PD-4 (PDF)-induced expression of fibrogenic cytokines in human peritoneal mesothelial cells (HPMCs), and to elucidate the mechanisms of action involved.

Methods: Seven groups of HPMCs were used in the study: control group, PDF group, T-IIA group, LY364947 group, and 2 transforming growth factor-β (TGF-β) groups (TGF-β+ 50 μM T-IIA and TGF-β+ 100 μM T- IIA). The expression levels of mRNA and protein of TGF-β, smad2, smad7, α-smooth muscle actin(α-SMA), fibronectin, collagen g0;, E-cadherin, N-cadherin, matrix metalloprotein-2(MMP-2), and MMP-9 in the various groups were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting as appropriate.

Results: The expressions of α-SMA, fibronectin, collagen g0;, TGF-β and smad2 were significantly up-regulated in HPMCs by PDF treatment, but smad7 was down-regulated, relative to the control group (p < 0.01).These PDF-induced effects were reversed by T-IIA (p < 0.05). Inhibition of TGF-β/smad pathway by LY364947 treatment led to significant decrease in the expressions of fibrosis-related proteins, when compared with PDF group (p < 0.05). TGF-β treatment also produced numerous spindle-shaped HPMCs characteristic of epithelial-mesenchymal transition (EMT). However, this morphological transition was alleviated, and the expression levels of EMT-related proteins were significantly down-regulated by exposure to the two doses of T-IIA (p < 0.05).

Conclusion: Tanshinone IIA inhibits EMT in HPMCs by regulating TGF-β/smad pathway, thus mitigating peritoneal fibrosis. Therefore, T-IIA has promising potential as a new drug for the treatment of peritoneal dialysis (PD)-induced fibrosis

Keywords: Peritoneal dialysis, Peritoneal fibrosis, Tanshinone IIA, Epithelial-mesenchymal transition