LXR agonists promote the proliferation of neural progenitor cells through MEK-ERK pathway

The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis and may be critical for neurodegeneration and neurogenesis in vivo. However, it remains largely unknown about the role of LXRs and its agonists in the in vitro proliferation of neural progenitor cells (NPCs). Here we revealed for the first time that LXRs were markedly expressed in mouse NPCs and were critical for the in vitro proliferation. LXR agonists GW3965 and LXR623 promoted the proliferation of wildtype NPCs, but not NPCs from LXR double-knockout mice. Mechanistically, phosphorylation of MEK1/2 and ERK1/2 in NPCs was enhanced upon LXR agonist treatment, while abrogation of MEK/ERK phosphorylation by the inhibitors PD98059 and U0126 impaired the proliferation of wildtype NPCs in the presence or absence of LXR agonists. Collectively, our findings suggest that LXR agonists GW3965 and LXR623 can stimulate the NPC proliferation in LXR- and MEK/ERK-dependent manner. - Highlights: • LXRs are expressed and functional in the mouse neural progenitor cells (NPCs). • LXRs are essential for the in vitro proliferation of mouse NPCs. • LXR agonists stimulate the proliferation of wildtype NPCs, but not LXRαβ−/− cells. • Phosphorylation of ERK/MEK was enhanced by LXR agonists in wildtype NPCs. • Inhibition of MEK/ERK phosphorylation impaired the proliferation of NPCs.