title: 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.
authors.affiliation: a Key Laboratory of TCM Pharmacology and Toxicology of Gansu Province , Gansu University of Traditional Chinese Medicine , Lanzhou 730000 , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Li
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wu
authors.forename: Mei
authors.initials: M
authors.lastname: Gu
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Li
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Wang
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Ming
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Dong
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005347:Fibroblasts / Q000528:radiation effects*; D005355:Fibrosis / Q000188:drug therapy; D006321:Heart / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D010616:Phenanthrenes; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; C024894:tanshinone II A sodium sulfonate; D003094:Collagen
keywords: ER stress; ROS; TGF-β1; cardiac fibroblasts; radiation-induced fibrosis damage