{Reference Type}: Journal Article
{Title}: Ac-SDKP promotes KIF3A-mediated β-catenin suppression through a ciliary mechanism to constrain silica-induced epithelial-myofibroblast transition.
{Author}: Liu S;Jin R;Zheng G;Wang Y;Li Q;Jin F;Li Y;Li T;Mao N;Wei Z;Li G;Fan Y;Xu H;Li S;Yang F;
{Journal}: Biomed Pharmacother
{Volume}: 166
{Issue}: 0
{Year}: 2023 Oct 29
{Factor}: 7.419
{DOI}: 10.1016/j.biopha.2023.115411
{Abstract}: Kinesin family member 3 A (KIF3A) decrease have been reported in silicotic patients and rats. However, the detailed mechanisms of KIF3A in silicosis remain unknown. In this study, we demonstrated that KIF3A effectively blocked the expression of β-catenin and downstream myocardin-related transcription factor (MRTF)-A/serum response factor (SRF) signaling, thus inhibiting silica-induced epithelial-myofibroblast transition (EMyT). Moreover, KIF3A was identified as a downstream mediator of an antifibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). Knockdown of KIF3A expression reactivated β-catenin/myocardin-related transcription factor (MRTF)-A/serum response factor (SRF) signaling that was attenuated by Ac-SDKP in vitro. Collectively, our findings suggest that Ac-SDKP plays its anti-fibrosis role via KIF3A-mediated β-catenin suppression, at least in part, in both in vivo model of silicosis and in vitro model of EMyT.