Affiliation:
1. Department of Dermatology Zhongshan Hospital Fudan University No. 180 Fenglin Road, Xuhui District Shanghai 200032 P. R. China
2. Department of Dermatology The First Hospital of Jiaxing & The Affiliated Hospital of Jiaxing University No. 1882 South Zhonghuan Road Jiaxing Zhejiang 314000 P. R. China
3. Department of Pharmacy Zhongshan Hospital Fudan University No. 180 Fenglin Road, Xuhui District Shanghai 200032 P. R. China
4. Shanghai Skin Disease Hospital Tongji University School of Medicine No. 1278 Baode Road Shanghai 200443 P. R. China
5. Institute of Clinical Science Zhongshan Hospital Fudan University No. 180 Fenglin Road, Xuhui District Shanghai 200032 P.R. China
Abstract
AbstractSystemic sclerosis (SSc) is an immune‐mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy with poor prognosis. Dangui Huoxue Preparation (DHP) is a clinically effective traditional Chinese herbal formula for the treatment of SSc in the hospital. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of DHP in the treatment of SSc. SSc mice models are induced by bleomycin (BLM). Tissues of DHP group, normal control group, and positive control drug Sanqi Tongshu Capsule (STC) group are collected for inflammation, fibrosis, and vasculopathy. Also, the human dermal fibroblasts (HDF) stimulated with TGF‐β1 are analyzed for in vitro study. The expression levels of MCP‐1, IFN‐γ, IL‐1β, IL‐10, Fizz1, iNOS, and IL12p40, and the mRNA levels of Col1a1, Col1a2, Col3a1, and Col5a1 are significantly decreased in all DHP groups and STC group compare with those in the BLM group. The main drug of DHP inhibits the proliferation and migration of HDF, reduces Ctgf, Itgb3, Itgb5 expression, and also inhibits the Smad3 pathway. In conclusion, DHP can ameliorate SSc skin inflammation, fibrosis, and vasculopathy, possibly suppressing the TGF‐β1/Smad3 signaling pathway through extracellular and intracellular mechanisms.
Funder
Natural Science Foundation of Shanghai Municipality