Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in cardiac fibroblasts

Abstract

The main pathological change in radiation-induced heart disease is fibrosis. Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was used for treating fibrosis diseases. The present study was undertaken to characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays, and the expression of TGF-β1 and collagen I (Col-1) increased, indicating that low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as an increase in the expression of the ER stress-related molecules, GRP78 and CHOP. Administration of STS reduced ROS production and decreased the expression of Col-1, TGF-β1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis damage was observed on a cellular level. The involvement of ER stress in radiation-induced fibrosis damage was demonstrated for the first time. STS attenuated the fibrosis damage effect in CFs and this effect may be related to its antioxidant action, and also related to its inhibition of ER stress and TGF-β1-Smad pathway. These results suggest that STS shows a good prospect in clinical prevention and treatment of RICF.

Keywords::

• radiation-induced fibrosis damage
• cardiac fibroblasts
• ROS
• ER stress
• TGF-β1

Funding

The work was supported by the Natural Science Foundation of Gansu Province of China [NO.1310RJZA088], Fundamental Research Funds for Gansu Universities of China [No.GZY2012-1],the Project of Key Laboratory of TCM Pharmacology and Toxicology of Gansu Province [NO.ZDSYS-ZZKJ-2013(B)-004],and Youth Foundation of Gansu university of Traditional Chinese Medicine [No. ZQ2011-15].