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 (PASMCs) 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 PASMCs of PAH rats, BU counteracted platelet-derived growth factor (PDGF)-induced Ki67 expression, and arrested the cell cycle, mainly at G0 /G1 . BU decreased proliferating cell nuclear antigen, c-Myc and cyclin D1 transcription and protein expression, while increasing p21 expression. BU reduced the transcription of PDGF receptor-β, and that of Ednra and Ednrb, 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 Akt phosphorylation, an effect reversed by the phosphatase inhibitor calyculin A. BU-treated cells showed a remarkable increase in acetylated Akt, indicating an inverse relationship between the levels of acetylated Akt and phospho-Akt. These findings may provide novel perspectives on the use of histone deacetylase inhibitors in PAH.

Cantoni S, Galletti M, Zambelli F, Valente S, Ponti F, Tassinari R, et al. (2013). Sodium butyrate inhibits platelet-derived growth factor-induced proliferation and migration in pulmonary artery smooth muscle cells through Akt inhibition. THE FEBS JOURNAL, 280(9), 2042-2055 [10.1111/febs.12227].

Sodium butyrate inhibits platelet-derived growth factor-induced proliferation and migration in pulmonary artery smooth muscle cells through Akt inhibition.

CANTONI, SILVIA;GALLETTI, MARGHERITA;VALENTE, SABRINA;PONTI, FRANCESCA;TASSINARI, RICCARDO;PASQUINELLI, GIANANDREA;GALIE', NAZZARENO;VENTURA, CARLO
2013

Abstract

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 (PASMCs) 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 PASMCs of PAH rats, BU counteracted platelet-derived growth factor (PDGF)-induced Ki67 expression, and arrested the cell cycle, mainly at G0 /G1 . BU decreased proliferating cell nuclear antigen, c-Myc and cyclin D1 transcription and protein expression, while increasing p21 expression. BU reduced the transcription of PDGF receptor-β, and that of Ednra and Ednrb, 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 Akt phosphorylation, an effect reversed by the phosphatase inhibitor calyculin A. BU-treated cells showed a remarkable increase in acetylated Akt, indicating an inverse relationship between the levels of acetylated Akt and phospho-Akt. These findings may provide novel perspectives on the use of histone deacetylase inhibitors in PAH.
2013
Cantoni S, Galletti M, Zambelli F, Valente S, Ponti F, Tassinari R, et al. (2013). Sodium butyrate inhibits platelet-derived growth factor-induced proliferation and migration in pulmonary artery smooth muscle cells through Akt inhibition. THE FEBS JOURNAL, 280(9), 2042-2055 [10.1111/febs.12227].
Cantoni S;Galletti M;Zambelli F;Valente S;Ponti F;Tassinari R;Pasquinelli G;Galiè N;Ventura C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/148908
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