2. Academic Validation
  3. SIS3, a specific inhibitor of smad3, attenuates bleomycin-induced pulmonary fibrosis in mice

SIS3, a specific inhibitor of smad3, attenuates bleomycin-induced pulmonary fibrosis in mice

  • Biochem Biophys Res Commun. 2018 Sep 5;503(2):757-762. doi: 10.1016/j.bbrc.2018.06.072.
Juanjuan Shou 1,  Jingjing Cao 1,  Shanshan Zhang 1,  Ruicong Sun 1,  Mengmeng Zhao 1,  Keqiang Chen 2,  Shao Bo Su 3,  Jianhua Yang 1,  Tianshu Yang 4
Affiliations

Affiliations

  • 1 Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Immunology, Tongji University School of Medicine, Shanghai, China.
  • 2 Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 3 Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
  • 4 Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Immunology, Tongji University School of Medicine, Shanghai, China. Electronic address: tianshuy@tongji.edu.cn.
PMID: 29913150 DOI: 10.1016/j.bbrc.2018.06.072
Abstract

Pulmonary fibrosis (PF) is a fatal respiratory disease with no effective medical treatments available. TGF-β/Smads signaling has been implicated to play an essential in the pathogenesis of PF, in which SMAD3 act as the integrator of pro-fibrosis signals. In this study, we determined the effect of SIS3, a specific inhibitor of SMAD3, in an experimental mouse model of lung fibrosis. We observed that SIS3 treatment significantly reduced bleomycin (BLM)-induced pathological changes and collagen deposition in the lung as indicated by Masson staining, Real-Time PCR and hydroxyproline content assay. As expected, the levels of SMAD3 phosphorylation were decreased in the lung of mice treated with SIS3. Furthermore, SIS3 treatment also suppressed BLM-induced infiltration of inflammatory cells in the lung. Taken together, our results suggest that SIS3 ameliorated BLM-induced PF in mouse lungs. Thus, targeting SMAD3 with SIS3 may be an effective approach for treatment of fibrotic disorders.

Keywords

Inflammation; Pulmonary fibrosis; Smad3; Transforming growth factor beta.

Figures
Products