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

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.072· OSTI ID:23136896

Shou, Juanjuan; Cao, Jingjing; Zhang, Shanshan; Sun, Ruicong; Zhao, Mengmeng ^[1]; Chen, Keqiang ^[1]; Su, Shao Bo ^[1]; Yang, Jianhua; Yang, Tianshu ^[1]

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1. Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai (China)

Highlights: • SIS3 ameliorate bleomycin-induced pulmonary fibrosis. • SIS3 reduced phosphorylation of Smad3 in lung of mice treated with bleomycin. • SIS3 suppressed acute lung inflammation induced by bleomycin. 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.

• OSTI ID: 23136896
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLEOMYCIN
COLLAGEN
FIBROSIS
GROWTH FACTORS
HYDROXYPROLINE
INFLAMMATION
LUNGS
MICE
PHOSPHORYLATION