Fig. 7.

Potential mechanism of PDGF-induced SphK1 expression and proliferation of hPASMCs in pulmonary arterial hypertension (PAH). The PDGF/PDGFR signaling pathway is upregulated in PAH. Activation of this pathway induces phosphorylation of MAPK/ERK, expression and nuclear translocation of the EGR1 transcription factor, and subsequent upregulation of SphK1 gene expression. Increased intracellular SphK1 may then lead to S1P production in hPASMCs, resulting in enhanced proliferation. Abnormal hPASMC proliferation leads to pulmonary vascular remodeling and increased pulmonary vascular resistance in PAH.