Sodium butyrate inhibits platelet‐derived growth factor‐induced proliferation and migration in pulmonary artery smooth muscle cells through A kt inhibition

• Published in: The FEBS journal 2013-05, Vol.280 (9), p.2042-2055
• Main Authors: Cantoni, Silvia, Galletti, Margherita, Zambelli, Filippo, Valente, Sabrina, Ponti, Francesca, Tassinari, Riccardo, Pasquinelli, Gianandrea, Galiè, Nazzareno, Ventura, Carlo
• Format: Article
• Language: English
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12227

Sodium butyrate ( BU ) is a molecule that acts as a histone deacetylase inhibitor. As compared with its well‐known antineoplastic/antiproliferative effects, little is known about BU action on vascular cell dynamics. An imbalance of proliferation and migration in pulmonary arterial smooth muscle cells ( PASMC s) is essential in the onset and progression of pulmonary arterial hypertension ( PAH ), a disease that is characterized by vascular lung derangement and that frequently has an unfavorable outcome. Here, we show that, in PASMC s of PAH rats, BU counteracted platelet‐derived growth factor ( PDGF )‐induced K i67 expression, and arrested the cell cycle, mainly at G 0 / G 1 . BU decreased proliferating cell nuclear antigen, c‐Myc and cyclin  D 1 transcription and protein expression, while increasing p21 expression. BU reduced the transcription of PDGF receptor‐β, and that of E dnra and E dnrb, two major receptors in PAH progression. Wound healing, migration and pulmonary artery ring assays indicated that BU inhibited PDGF ‐induced PASMC migration. BU strongly inhibited PDGF ‐induced A kt phosphorylation, an effect reversed by the phosphatase inhibitor calyculin A. BU ‐treated cells showed a remarkable increase in acetylated A kt, indicating an inverse relationship between the levels of acetylated A kt and phospho‐ A kt. These findings may provide novel perspectives on the use of histone deacetylase inhibitors in PAH .