Porcine placenta extract upregulates ceramide synthase 3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway

Abstract

AbstractPorcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of porcine placenta extract-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, porcine placenta extract-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect porcine placenta extract-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPAR δ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that porcine placenta extract induced phosphorylation of the STAT3 while porcine placenta extract-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that porcine placenta extract upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.