Peroxisome proliferator-activated receptor γ attenuates serotonin-induced pulmonary artery smooth muscle cell proliferation and apoptosis inhibition involving ERK1/2 pathway

• 5-HT can induce PASMCs proliferation and inhibit PASMCs apoptosis.
• 5-HT negatively regulated PPARγ expression and gene promoter activity in PASMCs.
• 5-HT induced PASMCs proliferation and apoptosis resistance can be abolished by PPARγ agonist and enhanced by PPARγ inhibitor.
• 5-HT-induced PPARγ expression inhibition is mediated by the ERK signaling pathway.

Serotonin (5-HT) has been shown to be involved in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) by inducing pulmonary artery smooth muscle cells (PASMCs) proliferation and inhibiting PASMC apoptosis. Peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in regulating proliferation and apoptosis of many cell types. Moreover, recently, loss of PPARγ has also been reported to be associated with the development of PAH. The present study is aimed to assess whether PPARγ is involved in 5-HT induced PASMC proliferation and apoptosis inhibition and the possible mechanism. We found that 5-HT could induce PASMC proliferation and inhibit PASMC apoptosis in a dose-dependent manner. Furthermore, we found that 5-HT negatively regulated PPARγ expression and gene promoter activity in PASMCs and 5-HT induced PASMC proliferation and apoptosis resistance could be abolished by PPARγ agonists and enhanced by PPARγ inhibitor. In addition, we found that extracellular signal-regulated kinase (ERK) signaling pathway mediated the 5-HT-induced inhibition of PPARγ expression. Our results might provide novel insights into the mechanisms for the pro-remodeling action of 5-HT in pulmonary vasculature.