title: Astragalus polysaccharide suppresses excessive collagen accumulation in a murine model of bleomycin-induced scleroderma.
abstract: Systemic scleroderma is an autoimmune disease characterized by fibrotic changes in skin and other organs involving excessive collagen deposition. The transforming growth factor-β (TGF-β) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Astragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. The present study aimed to investigate the effect of APS on TGF-β signaling and its potential mechanism using a murine model of bleomycin-induced scleroderma. Scleroderma was induced in C3H/He N mice by subcutaneous bleomycin injections daily for 21 days. Skin samples were obtained 7, 14, and 21 days and TGF-β1, Smad2, Smad3 mRNA expression was observed by real time PCR. The hydroxyproline content which consistent with the collagen content in skin samples from the BLM-injected group was significantly higher than the PBS group, and corresponded with dermal thickening at the injection site. In contrast, mice treated with APS after initiating BLM injection showed obviously lesser collagen content. Increased TGF-β1, Smad2, Smad3 mRNA expression were also observed in the BLM group. TGF-β1, Smad2, Smad3 expression was significantly lesser for the APS group than for the BLM group. In contrast, TGF-β1 mRNA expression was remarkably inhibited by APS. These results suggest that APS treatment may inhibit TGF-β1 production, and thus could be a potential drug for managing fibrotic disorders such as SSc.
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Region of PLA Beijing 100700, China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Hao
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Region of PLA Beijing 100700, China.
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Su
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Region of PLA Beijing 100700, China.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Region of PLA Beijing 100700, China.
authors.forename: Cong-Min
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Region of PLA Beijing 100700, China.
authors.forename: Rong-Ya
authors.initials: RY
authors.lastname: Yang
keywords: APS; Bleomycin-induced fibrosis; transforming growth factor-β1