Fig. 9.

DhSph driven increase in de novo sphingolipid synthesis inhibits collagen synthesis in NCFs by TGFβ. Exogenous dhSph drives the de novo sphingolipid synthesis pathway as indicated with the red arrows. DhCer and dhS1P (red squares) were increased the most. The increased activation of the de novo pathway was able to 1) inhibit TGFβ activated pSMAD2 and non-canonical pathway proteins such as pAkt and pRPS6, which also led to reduced expression of fibrotic gene markers such as TGFβ1 and TIMP1. (2) DhSph inhibited the S1PR1 agonist, SEW2871, induced collagen synthesis by reducing TGFβ1, TIMP1, CTGF, and TIMP2 mRNA expression, perhaps through a substrate- enzyme-receptor interaction. Illustrated using ChemDraw Professional 7.0 (Perkin Elmer, MA, USA).