SAHA could inhibit TGF-β1/p38 pathway in MI-induced cardiac fibrosis through DUSP4 overexpression

• Published in: Heart and vessels Vol. 37; no. 1; pp. 152 - 160
• Main Authors: Wang, Kaihao, Tang, Ruijie, Wang, Siyuan, Wang, Wenyao, Zhang, Kuo, Li, Jun, Li, Ping, Tang, Yi-Da
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.01.2022; Springer Nature B.V
• Subjects: Animals; Biomedical Engineering and Bioengineering; Cardiac Surgery; Cardiology; Cell proliferation; Fibroblasts; Fibrosis; Heart; Heart Diseases; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Hydroxamic acid; MAP Kinase Signaling System; Medicine; Medicine & Public Health; Mice; Original; Original Article; Phosphorylation; Protein Tyrosine Phosphatases; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b1; Vascular Surgery; Vorinostat - pharmacology; Western blotting; Cardiac fibrosis; TGF-β1; Dual-specificity phosphatase 4 (DUSP4); Suberoylanilide hydroxamic acid (SAHA)
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-021-01900-4

Growing evidences have revealed that a histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) has anti-fibrotic effect in different diseases. In this study, we first evaluated whether SAHA could suppress cardiac fibrosis. Mice with MI-induced cardiac fibrosis were treated with SAHA by intraperitoneal injection and their cardiac function was improved after SAHA treatment. Results of western blotting and qRT-PCR in heart tissues suggested that TGFβ1/P38 pathway was activated in MI mice, and this effect was reversed by SAHA. Cell proliferation assay suggested that SAHA could suppress TGF-β1-induced cardiac fibroblasts proliferation. Furthermore, results of western blotting and qRT-PCR in cardiac fibroblasts depicted that SAHA may exert its anti-fibrotic effect through inhibiting TGF-β1-induced P38 phosphorylation by promoting DUSP4 expression. Our findings may substantiate SAHA as a promising treatment for MI-induced cardiac fibrosis.